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Pathophysiology, Pharmacology, and Therapeutics > Exam 2 Concepts > Flashcards

Exam 2 Concepts Flashcards

1
Q

BMI

A

body weight in kilograms over (height in meters)^2

crude measure determine relative healthy body weight

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2
Q

obesity BMI

A 
>25>29.9 = overweight
>40 = morbid obesity
>50 = super morbid obesity
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3
Q

age to start BMI

A

36 months

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4
Q

greater predisposition to obesity

A

Native Americans
Pacific Islanders
African Americans
Latinos (Mexico and Puerto Rico)

more women than men

prevalence of obesity increases with age and declines after 60

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5
Q

location of obesity in U.S.

A

southern and midwestern states

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6
Q

genetics of obesity

A

leptin deficiency

Prader-Willi syndrome

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7
Q

environmental factors of obesity

A

increase in sugar, fat, salt (corn syrup)

increased portion sizes

fast food outlets

psychology manipulation by fast food industry

the “there-ness” of food - there and hard to say no

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8
Q

social factors of obesity

A

food deserts in inner cities

sedentary lifestyles

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9
Q

adipocyte definition

A

cells that store fat in the form of triglycerides. release triglycerides for energy/fuel purposes

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10
Q

adipocytes under conditions of energy excess

A

proliferate (hyperplasia)

hypertrophy: maladaptive response to energy excess

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11
Q

triglycerides definition

A

main storage form of fat

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12
Q

adiposopathy

A

hypertrophy of adipocytes in combination with visceral (organ) fat accumulation

aka “sick fat”

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13
Q

main patterns of fat deposition

A

central obesity - apple shape

peripheral obesity - pear shape

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14
Q

visceral fat definition

A

internal abdominal fat, located inside peritoneal cavity, packed between internal organs

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15
Q

subcutaneous fat definition

A

found under the skin

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16
Q

visceral fat pathology

A

fat deposited in and on organs, including heart, liver, and muscles, when capacity of adipocytes to store fat is exceeded

more hormonally active and more inflammation-promoting that subcutaneous fat

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17
Q

adipose tissue

A

organ cushioning
endocrine fxns

produces hormones and cytokines that contribute to inflammation, atherosclerosis, thrombosis, create conditions that develop and maintain obesity

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18
Q

leptin definition

A

increases satiety and energy expenditure

increases insulin sensitivity

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19
Q

leptin pathology

A

under conditions of increased/hypertrophied adipocytes, too much leptin is produced (“leptin resistance”)

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20
Q

adiponectin definition

A

hormone released from adipocytes

increases nitric oxide in vasculature, thereby increasing anti-atherogenic activities of vascular endothelium (prevents atherogenesis)

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21
Q

adiponectin pathology

A

as fat mass increases, amount of adiponectin decreases, promoting atherogenesis

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22
Q

atherogenesis definition

A

formation of subintimal lipid-containing plaques (atheromas) in lining of arteries

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23
Q

resistin definition

A

hormone release from adipocytes

increases insulin resistance

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24
Q

macrophage and monocyte chemoattractant protein-1 (MMCP-1)

A

hormone released from adipocytes

promotes inflammation by activating macrophages. increases insulin resistance.

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25
Q

TNF-alpha

A

hormone released from adipocytes

promotes inflammation and increases insulin resistance

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26
Q

plasminogen activator inhibitor-1

A

hormone released from adipocytes

inhibits breakdown of fibrin clots (pro thrombotic - pro clot-forming)

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27
Q

IL-6

A

hormone released from adipocytes

promotes inflammation
increases insulin resistance
increases hepatic lipid and glucose production

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28
Q

angiotensin II and aldosterone

A

hormones released from adipocytes

identified in adipose tissue –> hypertension

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29
Q

FFAs

A

free fatty acids
accumulate in obese people (intracellular)

toxic intermediates from the middle of the metabolic pathway hang around and overwhelm normal insulin signaling and muscle glucose transporter (GLUT4) fxns. excess FFAs contribute to insulin resistance

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30
Q

resulting pathologies of increased fat/adipocyte/adipose tissue

A 
inflammation
hypertension
atherosclerosis
thrombosis
atherogenic dyslipidemia
insulin-resistance
Type-2 diabetes
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31
Q

clinical manifestations and sequlae of obesity

A

central and/or peripheral obesity

dyslipidemia

cardiovascular disease

stroke

insulin resistance or frank diabetes

hypertension

cancer

sleep apnea

gallbladder disease

joint stress/osteoarthritis

NAFLD

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32
Q

dyslipidemia

A

includes hypertriglyceridemia accompanied by low HDL and smaller, denser LDL that are more pro-atherogenic (can get into arteries easier –> MI)

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33
Q

cardiovascular disease pathology in obesity

A

prothrombotic and atherogenic

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34
Q

stroke pathology in obesity

A

prothrombotic and atherogenic

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35
Q

frank diabetes

A

all the following markers of diabetes present, not just insulin resistance:

multiple hormones and cytokines released by adipocytes

excess FFAs

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36
Q

hypertension pathology in obesity

A

increased angiotensin II and aldosterone (vasoconstrictors)

decreaed NO

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37
Q

cancer pathology in obesity

A 
breast
endometrial
colon
kidney
esophageal
liver
pancreatic

cancer researchers call fat a carcinogen

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38
Q

sleep apnea pathology in obesity

A

increased upper airway pressure, reduced chest compliance related to truncal fat deposition

causes sleep deficit which decreases leptin and increases grehlin

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39
Q

grehlin definition

A

hormone produced by stomach that stimulates appetite

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40
Q

gallbladder disease pathology in obesity

A

accumulation of cholesterol

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41
Q

NAFLD definition

A

Nonalcoholic Fatty Liver Disease aka hepatic steatosis

triglycerides accumulate in liver cells, swelling and damaging the liver

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42
Q

NAFLD pathology in obesity

A

diseased liver cells resemble adipocytes

first hint of NAFLD: high levels of AST and LFTs (necrosis of liver cells)

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43
Q

obesity-related liver disease

A

liver disease progression. possible to move from 2 back to 1

  1. NAFLD
  2. NASH
  3. fibrosis progressing to cirrhosis
  4. hepatocellular carcinoma
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44
Q

NASH

A

non-alcoholic steatohepatitis

steatosis (fat accumulation) + inflammation (increased cytokine signaling)

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45
Q

genetic influences in NAFLD

A

Latinos particularly vulnerable

carry a variant of gene PNPLA3 that results in high liver fat content

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46
Q

pathology of BMI over 35

A

quick rise in mortality compared to lower end of BMI spectrum

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47
Q

obese children

A
  • high risk of diabetes
  • high risk of becoming obese adults
  • develop NAFLD (#1 cause of chronic liver disease in children)
  • early evidence of atherosclerosis
  • metabolic syndrome
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48
Q

metabolic syndrome definition

A

(MetS): constellation of symptoms that increases risk of cardiovascular disease. closely related to obesity but not the same thing. 3 of 5 characteristics

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49
Q

5 characteristics of MetS

A 
large waist size
high TGs
low good cholesterol
high BP
high fasting serum glucose
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50
Q

symptoms related to MetS

A

central obesity
dyslipidemia (w/ decreased HDL)
increased BP
hyperglycemia

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51
Q

why care about MetS?

A

red-warning flag

continuum from preventing to managing to managing comorbidities to death

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52
Q

lipogenesis

A

formation of new lipid (usually via metabolism of glucose by acetyl CoA)

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53
Q

intake > output

A

excess ingested glucose used for lipogenesis

excess ingested fat directly deposited in adipocytes

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54
Q

insulin in obesity

A

main anabolic hormone of body. promotes cellular uptake of glucose, storage of TGs in adipose tissue, and other processes

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55
Q

without insulin

A

glucose cannot enter cells and fat deposition in adipose tissue is impaired

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56
Q

glycogen

A

storage form of glucose in liver

stored by liver

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57
Q

where fat comes from

A

glucose not used/stored by liver metabolized by acetyl CoA to synthesize triglyceride and cholesterol

liver packages TFs and fatty acids into VLDL

adipose cells take up glucose via GLUT 4 receptor for energy needs and to synthesize fatty acids and TGs

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58
Q

end result of glucose

A

lipids (cholesterol and TGs)

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59
Q

fructose

A

part of disaccharide sucrose

more likely to be converted to fat than glucose

its biochemical metabolic pathway preferentially leads to the production of fat

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60
Q

chylomicrons

A

lipoproteins made outside of the liver (in the small intestine) from absorbed dietary fats that travel to the thoracic duct to enter the bloodstream

travel in circulation to deliver fat (mostly TGs) to tissues

  • fats broken down by lipoprotein lipase
  • fatty acids diffuse into adipocytes to reform TGs
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61
Q

lipoprotein lipase

A

enzyme found on vascular endothelial cells throughout the body (particularly in adipose tissue) that breaks down TGs from VLDLs and chylomicrons into fatty acids that can diffuse into adipocyte

once in the adipocyte, the TGs are reformed and stored

insulin promotes activity of lipoprotein lipase - insulin is hormone that promotes fat storage

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62
Q

hormone-sensitive lipase

A

enzyme that promotes the breakdown of stored TGs so the adipocyte can release free fatty acids and glycerol

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63
Q

lipoprotein definition

A

any of a number of complex molecules that consist of a protein membrane surrounding a core of lipids

carry cholesterol and other lipids from digestive tract to liver and other tissues

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64
Q

VLDL

A

(very low density lipoprotein)

primarily delivers TGs to tissues

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65
Q

LDL

A

(low density lipoprotein)

primarily delivers cholesterol to tissues
plays major role in atherogenesis in blood vessels
-which is why it’s called “bad cholesterol”

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66
Q

HDL

A

(high density lipoprotein)

carries out out reverse cholesterol transport and brings cholesterol back to liver
-which is why it’s called “good cholesterol”

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67
Q

lipoprotein structure

A

generalized structure of a non-polar (hydrophobic) core of TGs and cholesterol esters surrounded by hydrophilic shell of phospholipids (most abundant constituent part), non-esterfied cholesterol and apoproteins

hydrophilic shell allows lipoproteins to travel in plasma

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68
Q

dyslipidemia

A

abnormal blood lipid panel

high TGs and/or high VLDL or LDL and/or low HDL

used interchangeably with hyperlipidemia (most focused on)

excess fatty acids can contribute to insulin resistance

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69
Q

insulin resistance

A

may activate adipose tissue hormone-sensitive lipase and inhibit lipoprotein lipase
-increase VLDL levels

hormone-sensitive lipase sends more fatty acids to liver to be packaged into VLDLs

lipoprotein lipase can no longer break down TGs from VLDLs and chylomicrons for diffusion in adipocytes

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70
Q

fate of fatty acids and glycerol in liver

A

liver synthesizes new lipids from products of lipolysis

glycerol can be used to form new glucose

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71
Q

atherosclerosis definition

A

complex process by which arteries become progressively narrowed, impairing supply of oxygen and nutrients to tissues

involves deposition of lipoproteins (particularly LDL-C), macrophages, inflammatory mediators and smooth muscle cells in tunica intima layer of arteries; formation of plaques

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72
Q

atherosclerosis pathology

A

impaired blood flow can result in ischemia and cause angina or intermittent claudication

atherosclerotic plaques can rupture, triggering acute formation of clot, and abrupt loss of blood supply to tissues - resulting in MI

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73
Q

intermittent claudication

A

walking and legs start to hurt because muscles aren’t getting enough oxygen (especially lower legs)

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74
Q

statins

A

HMG-CoA-reductase inhibitors

decrease LDL
decrease TGs
increase HDL

stabilize atherosclerotic plaques

most effective for lowering LDL and total cholesterol. only medication for managing cardiovascular risk

somewhat controversial

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75
Q

PCSK9 inhibitors

A

proprotein convertase subtilisin-kexin type 9

monoclonal antibodies that block PCSK9 that normally binds to LDL receptor and prevents it from returning to surface to take in more LDL from the blood
-med allows constant recycling of LDL which drastically lowers serum cholestrol levels

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76
Q

glucose

A

polar and hydrophilic

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77
Q

glucose diffusion

A

facilitated diffusion down concentration gradient (e>i)

sometimes against concentration gradient via secondary active transport (SGLT) with sodium (occurs in renal tubes)

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78
Q

GLUT 2 on liver cells

A

after eating:
glucose is high in liver blood supply and low in intracellular fluid, so GLUT 2 moves glucose into liver cell

while fasting:
liver cells make glucose via glycogenolysis and gluconeogenesis which raises glucose levels inside liver cell, so GLUT 2 moves glucose to extracellular fluid of liver cell and ultimately to bloodstream

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79
Q

GLUT 4

A

sensitive to insulin
found mostly on muscle and fat cells - translocation to cell membrane stimulated by insulin-receptor interaction

translocation also enhanced by muscle contraction during exercise (i.e. exercise can improve insulin sensitivity)

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80
Q

GLUT 4 on muscle cells

A

after eating:
glucose and insulin levels increase, so GLUT 4 translocate to muscle cell membrane to move glucose into cell (moves because of signal created by insulin)

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81
Q

glucosuria

A

glucose in the urine

occurs when hyperglycemia levels in DM overwhelm transporters in renal tubes, leading to persistent urinary glucose

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82
Q

glucose as energy source

A

converted to glucose-6-phosphate (G6P) by hexokinase or glucokinase when it enters cells

G6P undergoes glycolysis, producing pyruvate

pyruvate enters mito

w/ oxxygen, pyruvate converted to acetyl CoA, which enters Krebs cycle

electron transport produces most ATP

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83
Q

liver processes during fed state (w. insulin present)

A
  • glucose uptake and glycogenesis (glycogen synthesis)
  • glycolysis, forming acetyl CoA

Acetyl CoA used to synthesize:

  • triglyceride (lipogenesis) forming VLDLs
  • cholesterol
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84
Q

adipose processes during fed state (w. insulin present)

A

glucose uptake via GLUT 4

triglyceride uptake via lipoprotein lipase and storage

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85
Q

muscle processes during fed state (w. insulin present)

A

glucose uptake via GLUT 4 and amino acids (facilitated by insulin)

protein and glycogen synthesis

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86
Q

processes during fasting

A

hepatic glucose production depends on ability to produce G6P and ability to remove phosphate, releasing free glucose

glucose entry into ALL cells is followed by phosphorylation, trapping G6P inside cell
-in liver cells, this is reversible because of G6-phosphatase enzyme

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87
Q

glucose phosphorylation and dephosphorylation

A

All cells:
glucose + phosphate
–> glucose-6-phosphate
(G6P trapped in cell)

Liver and kidney cells:
glucose-6-phosphate
–> glucose + phosphate
(free glucose that can be transported outside cell)

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88
Q

pathways of hepatic glucose production

A

glycogenolysis

gluconeogenesis (also in kidney)

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89
Q

glycogenolysis in liver

A

breakdown of glycogen to produce G6P. G6-phosphatase removes phosphate, generating free glucose that can be transported into blood stream

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90
Q

gluconeogenesis in liver

A

substrates generated by liver, muscle, fat can enter pathway to synthesize new glucose

precursors include: lactate and amino acids from muscle, glycerol from fat

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91
Q

precursors for hepatic gluconeogenesis

A

amino acids - from muscle proteolysis

lactate - from muscle glycogenolysis

glycerol - from adipose lipolysis

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92
Q

catabolic pathways in muscle

A

glycogenolysis

proteolysis

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93
Q

glycogenolysis in muscle

A

breakdown of muscle glycogen to G6P

G6P not dephosphorylated - undergoes glycolysis and converted to lactate

lactate travels through bloodstream to liver as precursor to gluconeogenesis

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94
Q

proteolysis in muscle

A

protein breakdown releases amino acids to be used as precursor for gluconeogenesis

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95
Q

precursors released by muscle for liver gluconeogenesis

A

lactate (glycogenolysis)

amino acids (proteolysis)

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96
Q

lipolysis in adipose tissue

A

decreased insulin, increase epi, increased cortisol
–> activates fat breakdown via hormone-sensitive lipase (HSL)

  • TG broken down to glycerol + 3 fatty acids
  • glycerol travels to liver for gluconeogenesis
  • fatty acids travel via circulation to
    • muscle for fuel
    • liver for fuel and production of ketone bodies
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97
Q

ketogenesis

A

a liver catabolic pathway that depends on adipose lipolysis

fatty acids released by adipose lipolysis become oxidized by liver at high rate to produce ketone bodies

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98
Q

liver ketogenesis is favored by

A

prolonged fasting
absence of insulin
low carb diet
high levels of glucagon and stress hormones

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99
Q

ketone bodies

A

acetoacetate
beta-hydroxybutyrate

can be used by brain and many tissues for fuel, but create metabolic acidosis

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100
Q

conditions favoring ketone body formation

A

hormone balance:

  • increased glucagon/counter-insulin hormones
  • decrease/absent insulin

adipose tissue:
accelerated lipolysis

liver:

  • fatty acid oxidation increases Acetyl CoA
  • Acetyl CoA synthesizes ketone bodies

prolonged fasting and/or low carb intake

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101
Q

counter-insulin hormones =

A

stress hormones

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102
Q

hormonal regulation of glucose metabolism

A

insulin synthesized in pancreas by B-cells of islets of Langerhans

B-cells produce proinsulin, which is stored in granules and cleaved into insulin and c-peptide

a-cells produce glucagon

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103
Q

islet of Langerhans

A

cluster of pancreatic endocrine cells

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104
Q

insulin molecule

A

protein hormone with A chain and B chain joined by disulfide bonds

connecting peptide has two a.a. cleaved from each end by peptidase enzyme to create C peptide (secreted with insulin)

c-peptide assay used to measure endogenous insulin production (no C-peptide = no insulin)

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105
Q

insulin secretion overview

A

increased plasma glucose is primary stimulus for insulin release

glucose enters B cells passively through GLUT 2

glucose triggers chain of events that results in exocytosis of insulin

insulin binds to receptor on insulin-sensitive cells and triggers glucose uptake via GLUT 4

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106
Q

first phase of insulin secretion

A

glucose in food causes brief rise in insulin release/secretion (short term)

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107
Q

second phase of insulin secretion

A

continued glucose presence causes insulin production (long term)

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108
Q

incretin effect

A

ingestion of nutrient stimulates release of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) from cells in gut

GIP and GLP-1 stimulate production of insulin and GLP-1 also inhibits glucagon

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109
Q

steps involved in insulin secretion

A
  1. glucose enters cell via GLUT2 - phosphate added by glucokinase
  2. G6P oxidized, producing ATP
  3. ATP closes ATP-sensitive potassium channel (sulfonylurea-sensitive)
  4. cell depolarizes, activating voltage-gated calcium channels
  5. calcium entry = signal for insulin secretion via exocytosis
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110
Q

insulin actions on liver

A

increases glycogen storage and glycolysis

increases TG synthesis and release (VLDL)

inhibits gluconeogenesis and ketone production

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111
Q

insulin actions on muscle

A

increases uptake, storage and use of glucose. storage form = glycogen

increases uptake of a.a. and protein synthesis

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112
Q

insulin actions on fat

A

stimulates lipoprotein lipase and TG synthesis and storage

strongly inhibits hormone-sensitive lipase (which would cause lipolysis)

increases uptake and use of glucose

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113
Q

intraislet paracrine action

A

inhibits glucagon secretion

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114
Q

glucagon during fasting state

A

dominant hormone

responsible for most glucose production during fasting state

source: alpha cells

inhibited by insulin (paracrine effect), GLP-1, glucose at sufficient levels

“counter-regulatory” or “counter-insulin” hormone

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115
Q

glucagon actions on liver

A

increases glycogenolysis: glycogen breakdown

increases gluconeogenesis: new glucose

increases ketone body formation: ketogenesis

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116
Q

cortisol

A

counter-insulin hormone

  • released during stress
  • increases hepatic gluconeogenesis
  • promotes muscle proteolysis, increasing amino acid pool for glucose production
  • at high levels, promotes lipolysis, increasing free fatty acids and glycerol
  • overall effect is to promote glucose production and release

note the hyperglycemic effects of glucocorticoid medications

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117
Q

metabolic actions of epinephrine

A

stress/anti-insulin hormone

liver: intracellular MOA to increase glycogenolysis, gluconeogenesis, ketogenesis, inhibit glycogenesis

adipose: decrease TG synthesis, stimulates lipolysis
(–> ketone production)

muscle: suppress glucose uptake, stimulates glycolysis with release of lactate into circulation

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118
Q

anti-insulin hormones complicate blood glucose regulation in hospitalized patients

A
  • stress hormones can increase blood glucose levels
  • glucocorticoids can exacerbate situation
  • increased blood glucose can delay healing time
  • insulin-dependent diabetics may require more insulin than usual
  • non-insulin-dependent diabetics may require insulin
  • even some non-diabetics may temporarily require insulin
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119
Q

growth hormone

A

anti-insulin hormone

released during hypoglycemia

GH excess (acromegaly) results in diabetes

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120
Q

chorionic somatomammotropin

A

(pregnancy - anti-insulin hormone)

gestational diabetes

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121
Q

genetics of DM

A

some heritable tendency in T1DM but greater in T2DM

  • still some work to determine genetic variations that make people more susceptible to T1DM
  • hard to tease out “pure” genetic factors from environmental factors in T2DM
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122
Q

genome-wide association studies

A

majority of genes implicated in immune response (autoimmunity - T1DM) are HLA genes
–most associations are weak

in T2DM, more complex mixture of potential pathways are being studied

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123
Q

timeline of T1DM

A

peak onset between 11 and 13

possible precipitating event: viral infection (occurs a lot in autoimmune disorders)

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124
Q

classic DM presentation

A 
polyuria - excessive urinary output
polydipsia - excessive thirst
polyphagia - excessive eating
weight loss
hyperglycemia and hyperlipidemia

DUE TO;
absence of insulin (T1) OR
lack of effective insulin coupled with insulin deficiency (T2)

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125
Q

clinical presentation of T1DM

A
  • patients often extremely ill and may be in diabetic ketoacidosis
  • 3 “polys”
  • ketone formation due to unopposed glucagon action
    • contributes to osmotic diuresis, and metabolic acidosis
  • weight loss, fatigue
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126
Q

What causes the 3 “polys”?

A

hyperglycemia overwhelms the kidneys’ ability to reabsorb glucose

leads to osmotic diuresis (water follows glucose into urine) and excessive urination (polyuria) which leads to dehydration which leads to thirst reaction (polydipsia)

loss of satiety signals, primarily insulin, leads to polyphagia. body also perceives starvation because glucose cannot get into cells

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127
Q

diabetic ketoacidosis (DKA)

A
  • precipitating event
  • severe hyperglycemia but perceived by the body as starving for glucose, so liver continues to make glucose (stimulated by glucagon not insulin)
  • adipose tissue only sees glucagon, epi, and cortisol, which activates hormone-sensitive lipase and metabolizes TGs into FFA and glycerol into blood stream
  • liver takes up glycerol for glucose and FFA for ketone bodies
  • muscle releases lactate and a.a. for liver gluconeogenesis
  • stress hormones worsen hyperglycemia
  • kidneys overwhelmed by hyperglycemia, which spills glucose into urine, followed by water –> dehydration
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128
Q

hospital management of DKA

A

isotonic fluids
insulin
K+
glucose later

without management, patient will become comatose and die

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129
Q

hypoglycemia in T1DM

A
  • reduced counterregulatory responses (no glucagon response, decreased epi and cortisol responses)
  • hypoglycemia unawareness
  • worse after exercise and during sleep (coma and seizures)
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130
Q

T2DM overview

A
  • incidence increases with age; familial connection; obesity closely linked
  • decreased insulin secretion accompanied by insulin resistance and eventual B-cell dysfunction
  • glucagon secreted at high levels, increasing hepatic glucose production
  • often preceded by prediabetes, indicated by impaired glucose tolerance (IGT) and impaired fasting glucose (IFG)
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131
Q

double whammy of T2DM

A

insulin resistance: hyperglycemia and dysregulation of liver glucose production

high glucagon levels: insulin not exerting paracrine effect on Islets of Langerhans (excessive glucagon tells liver to produce excess glucose)

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132
Q

pancreatic cells in T2DM

A

initially respond to insulin resistance with hyperplasia and hypersecretion of insulin - maintains euglycemia for some time

B-cells are worked to death, leading to frank insulin deficiency. patients may require more and more insulin as disease progresses

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133
Q

hemoglobin A1c

A

formed when N-terminal valine of beta chains of hemoglobin A is modified by addition of glucose

resulting molecule is stable and can be measured

algorithm convers percentage of A1c in serum to an average blood glucose over ~last 3 months (blood glucose is attached to erythrocytes, which have a lifespan of ~3 months)

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134
Q

monitoring A1c

A

ADA recommends A1c less than 7%
AACE recommends 6.5% or less

healthy older adults: 7.5
complex/intermediate older adults: 8.0
older adults in poor health: 8.5

worried about hypoglycemia and falls in older adults

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135
Q

hyperosmolar hyperglycemic state (HHS)

A

precipitating event (usually infection - 60%) that decreases fluid intake and increases insensible loss, leading to increased stress hormone secretion

hyperglycemia is extreme, but lack of metabolic acidosis does not make patients sick enough to seek help

greater fluid loss than DKA

hyperosmolar state with severe intracellular dehydration

low level of insulin preventse ketosis

136
Q

DKA vs HHS

A 
in HHS:
higher blood glucose
higher bicarb (more ketone bodies so body is trying to normalize pH with bicarb)
higher pH
low insulin (vs. absent)
greater fluid loss
137
Q

T2DM acute complications

A

long-term T2DM can develop DKA, but less common than in T1

hypoglycemia less common, but can occur with insulin, secretagogues, older adults

138
Q

nonpharmacologic management of T2DM

A 
diet and weight loss
increase physical activity
reduce stress
increase sleep
assess/treat depression
139
Q

chronic DM complicatons

A

microvascular:
retinopathy
nephropathy

macrovascular:
dyslipidemia

neuropathy:
polyneuropathy (distal pain)
autonomic neuropathy (orthostatic hypotension, tachycardia, silent MI, sexual dysfxn)

foot ulcers (neuropathy + vessel disease + poor wound healing)

infections

140
Q

diabetic retinopathy

A

thickening of retinal capillaries
microinfarcts
microaneurysms
comorbid hypertension

141
Q

hypoglycemia risk factors

A

mismatch of insulin timing, amount, or type for carb intake

oral secretagogues w/o sufficient carb intake

reduction in nutrient intake

  • NPO
  • not finishing meal/snack
  • IV carb discontinued/decreased
  • interruption of enteral feeding

nausea/vomiting

geriatric patieqnts at higher risk

142
Q

Somogyi Effect

A

undetected hypoglycemia early in the morning )(2/2 PM intermediate NPH dose peak) followed by hyperglycemia later in the morning

confirm with 3am BG or 3-day continuous glucose monitoring system

143
Q

Dawn Phenomenon

A

rise in BG between 4-8am 2/2 counterregulatory hormones that are normally released

hyperglycemia in morning

check 3am BG

  • hypoglycemia = Somogyi
  • hyperglycemia = Dawn
  • euglycemia = more checks
144
Q

patient/family teaching about insulin

A

store unopened vials or pens in refrigerator; do not freeze

current vial/pen can be stored at room temp for 1 mo

suspension forms (NPH) should be rolled gently between palms; do not shake

cloudy insulin should be discarded

swab top of vial with alcohol prior to syringe

clear skin before injection and allow alcohol to dry

inject in subQ fat of abdomen, upper arm or upper/lateral thigh

rotate injection sites

do not reuse syringes/pens

teach S/Sx of hypoglycemia and how to manage (carry quick source of glucose)

pts must eat if using rapid- or short-acting insulin

glucometer, especially when sick

calculate carbs and adjust bolus

medical alert bracelet

145
Q

peripheral circulation highlights

A
  • parallel circuits
  • variation in regional flow
  • increased flow in active tissues
  • decreased flow in inactive tissues
  • maintained flow to vital organs
  • limit change to systemic flow on minute-to-minute basis
146
Q

stroke volume

A

SV

amount of blood ejected from the ventricle with each contraction (LV or RV, usually LV)

147
Q

systemic vascular resistance

A

SVR (also TPR)

resistance to blood flow offered by all of the systemic vasculature, excluding pulmonary vasculature

148
Q

vasoconstriction on SVR

A

increases SVR

149
Q

vasodilation on SVR

A

decreases SVR

150
Q

what determines blood pressure?

A

mean arterial pressure =
CO * SVR

CO = HR * SV

mean pulmonary artery pressure =
CO * pulmonary vascular resistance

151
Q

how is systemic mean arterial pressure estimated clinically from SBP and DBP?

A

DP + (SP-DP)/3

diastole takes 2X as much time to occur than systole

152
Q

SA node innervated by…

A

right vagus nerve

153
Q

AV node innervated by…

A

left vagus nerve

154
Q

autonomic nervous system in HR regulation

A

parasympathetic (vagus nerve, acetylcholine):

  • slow heart
  • acetylcholine acts at muscarinic receptors
  • resting state under control of vagus nerve (vagal tone)

sympathetic:

  • speeds up heart
  • norepinephrine acts at B1 adrenergic receptors (dominated by B1 over B2)
155
Q

training/conditioning in regulation of HR

A

slower resting HR

maintaining CO

156
Q

determinants of stroke volume

A

preload
afterload
contractility

157
Q

preload

A

amount of blood filling heart right before it starts to contract (EDV)

158
Q

determining factors of preload

A

blood volume and body volume: decrease volume, decrease preload (vice versa)

ability of ventricle to relax normally during diastole

venoconstriction via symp. nervous system: squeezes blood toward heart

muscular pump in calf returning blood to heart

increased preload lead to increased stretch of cardiac sarcomeres leads to stronger contraction leads to increased SV

increase/decrease preload, increase/decrease SV

159
Q

amount of blood in venous system at any one time

A

3/4

160
Q

afterload

A

pressure that the ventricle sees after it starts to contract. force that has to be overcome to pump blood into systemic circulation

in LV, working to open aortic valve and working against diastolic presure in aorta

161
Q

determining factors of afterload

A

systemic vascular resistance and aortic pressure

valve integrity

increase afterload, decrease SV

decrease afterload, increase SV

162
Q

contractility

A

intrinsic strength of cardiac contraction. force with which the ventricle contracts

163
Q

determining factors of contractility

A

sympathetic control of ventricle (norepinephrine, B1)

activation of B1 receptors leads to increased contractility

conditioning/training improves performance

increase/decrease contractility, increase/decrease SV

164
Q

determinants of SVR

A

vessel radius, length, and blood viscosity
-mostly radius (1/r^4)

arterioles (radius): controlled by

  • symp. nervous system (a1-adrenergic mediated constrxn (prevents orthostatic hypotension)
  • voltage gated calcium channels on smooth muscle: increased calcium flow to cause vasoconstriction
  • receptors for hormones and loacl mediators
165
Q

which tunica is composed of primarily smooth muscle?

A

tunica media

166
Q

tunica of arterioles

A

tunica interna
tunica media
tunica externa

167
Q

why are arterioles major blood vessel type that influences SVR?

A

blood flow becomes steady, not pulsing

168
Q

hormonal determinants of SVR

A

constrictors:

  • angiotensin II (RAAS - kidney) -increases aldosterone which conserves sodium and blood volume
  • vasopressin/ADH (posterior pituitary) - kidneys conserve water and blood volume, vasoconstriction of smooth muscle
  • endothelin (endothelium) - locally constricts blood vessels

dilators:

  • nitric oxide (endothelium) - locally dilates blood vessels
  • ANP, BNP (when heart is stretched) - sense heart stretch, increase natriuresis in kidney (Na excretion), vasodilation in smooth muscle
  • B-adrenergic receptors in some vascular beds
169
Q

short-term control of BP

A

largely controlled by baroreceptors

170
Q

vasomotor center

A

in medulla
directly activated by various stimuli or indirectly via baroreceptors which monitor MAP variations on a moment-by-moment basis

171
Q

baroreceptors

A

arch of aorta

carotid artery sinuses

172
Q

baroreceptor reflex

A

changes in MAP initiated by baroreceptors

can be downregulated after even a relatively short hospital stay

173
Q

decrease in MAP results in:

A

activation of:

  • a1-receptors in smooth muscle of arterioles (vasoconstriction)
  • B1 receptors in heart (increase HR)
174
Q

normotension

A

BP

175
Q

hypertension

A

BP > 140/90

176
Q

essential hypertension

A

common, correlated with prevalence of obesity and diet high in fats and sodium

most idiopathic

managed with lifestyle and pharmacological approaches

177
Q

prehypertension

A

systolic 120-139, diastolic 80-89

178
Q

potentially treatable causes of hypertension

A

(~10% of cases)

  • chronic kidney disease
  • renovascular
  • endocrine
    • aldosterone excess
    • pheochromocytoma (tumor produces epi)
    • cortisol excess (Cushing’s disease)
179
Q

pulmonary hypertension

A

one cause of right heart failure

more common in women

primary PH - poorly understood

idiopathic

secondary to chronic lung disease

180
Q

systemic arterial hypertension risk factors

A
  • family history
  • older age
  • obesity
  • increased dietary sodium and decreased calcium, potassium, magnesium
  • smoking (nicotine = vasoconstrictor)
  • African American
  • excessive alcohol consumption
  • social determinants of health
181
Q

clinical manifestations of hypertension

A
  • may be asymptomatic for years
  • may have headaches but nonspecific
  • organ damage w.o treatment
  • white coat hypertension
182
Q

cellular dysfxn in essential hypertension

A

two hypotheses:

  1. defect of vascular smooth muscle with abnormal reactivity, possibly also made worse by stress –> vascular resistance increases
  2. defect of renal sodium excretion –> body fluid vol. increases, BP increases
183
Q

lifestyle approaches to managing hypertension

A
  • Na restriction
  • DASH diet
  • alcohol reduction
  • exercise
  • stop smoking
  • K+ Ca++ intake
  • recognize barriers to adherence and principles of behavior change
184
Q

hypertension: end-organ effects

A 
heart and circulation (arteries)
kidneys
brain
eyes
reproductive system (i.e. erectile dysfxn)
185
Q

arteriosclerosis

A

hardening and stenosis of arteries where they become less flexible due to collagen deposition (general)

increased pulse pressure: SBP-DBP

186
Q

atheroclerosis

A

development of a plaque in focal areas via cholesterol deposition

187
Q

hypertension on renal arterioles

A

hypertrophy, constriction

188
Q

hypertension on brain

A

hemorrhage

189
Q

hypertension on eyes

A

retinopathy:

  • hemorrhage
  • cotton wool spots
  • hard exudates
190
Q

Starling’s Law of the Heart

A

increased preload –> increased SV

191
Q

contractility influences position of Frank-Starling Curve

A
  • SNS activity increases contractility, shifting curve up: greater SV at any given ventricular end-diastolic volume
  • HF shifts curve down. Higher and higher levels of preload do not lead to normal stroke volumes, but do increae workoad of heart
192
Q

determinants of blood volume

A

part of extracellular fluid compartment

sodium intake

hormonal regulation of Na and water retention or excretion by kidneys allows fine-tuning

  • aldosterone regulates Na (increases retention, increases water retention/volume)
  • vasopressin/ADH: regulates water
  • natriuretic peptides (ANP, BNP): regulate sodium (increase excretion, decrease water retention, decrease volume
193
Q

heart failure concepts

A

not a single disease - syndrome with common findings regardless of etiology

defined as inability of heart to produce enough CO to meet needs of body

left HF more common, most common cause of R HF

isolated right HF often 2/2 lung disease

late stages, most patients biventricular failure

194
Q

ejection fraction

A

SV/LVEDV

fraction of blood volume from the ventricle at end of diastole that is actually ejected into systemic circulation

195
Q

systolic heart failure

A

impaired ability of the ventricle to contract, reducing SV and EF to ,40% (normally 55-70%)

generally occurs due to weakened heart wall

196
Q

remodeling

A

best described in systolic failure

wall of ventricle thins, chamber gets larger (increase in volume, but decrease in pressure). myocytes die and replaced with stiff, fibrotic tissue, ventricle dilates

no longer has good shape for contracting/pumping

generally occurs due to chronically increased preload

197
Q

ventricular wall thinning due to

A

chronically increased preload

198
Q

ventricular wall thickening due to

A

chronically increased afterload

199
Q

etiology of systolic HF

A
  • coronary artery disease/MI
  • hypertension
  • valve disorders
  • familial/genetic - dilated cardiomyopathy
  • toxic damage
  • idiopathic
200
Q

diastolic remodeling

A

increase wall tension

increase preload/afterload

201
Q

systolic remodeling

A

death of myocardial cells

202
Q

dilated cardiomyopathy

A

not the same as systolic HF

condition where heart becomes enormous and can’t pump

203
Q

diastolic heart failure

A

impaired relaxation of the ventricle decreases the amount of filling and end-diastolic volume. ventricle wall is too stiff. ventricular hypertrophy is a common cause of diastolic failure.

even though contractility and ejection fraction are normal, SV is decreased due to poor filling

204
Q

etiology of diastolic HF

A
  • secondary hypertrophy (hypertension)
  • aging
  • ischemic fibrosis
  • hypertrophic caridiomyopathy
205
Q

hypertrophic cardiomyopathy

A
  • genetic disease
  • second decade of life or later
  • abnormal thickening or enlargement of ventricular walls, obstruction of blood flow at the left ventricular outflow tract, sarcomere disarray
  • HCM clinical presentation: heart failure, syncope, arrhythmia
  • leading cause of sudden death in young athletes
206
Q

high output HF

A

when the needs of the body are increased

ex: hyperthyroidism in older person, severe anemia, some kidney failure

need to treat precipitating cause

207
Q

Classification Scheme - NYHA

A

patients may go back and forth in stages, depending on symptoms

208
Q

Class I HF

A

no incapacity

although patient has heart disease, fxnal capacity is not sufficiently impaired to produce symptoms

209
Q

Class II HF

A

slight limitation

patient is comfortable at rest and with mild exertion. symptoms occur only with more strenuous activity

210
Q

Class III HF

A

incapacity w. slight exertion

patient is comfortable at rest by dyspnea, fatigue, palpitation, or angina appears with slight exertion

211
Q

Class IV HF

A

incapacity with rest

slightest exertion invariably produces symptoms, symptoms frequenly occur at rest

212
Q

Classification Scheme ACC/AHA

A

based on history, risk factors, and structural changes, emphasizes progression among stages (not necessarily true for symptoms)

213
Q

Stage A

A

patients at high risk for heart failure but without structural heart disease or symptoms of heart failure

214
Q

Stage B

A

patients with structural heart disease but without signs or symptoms of heart failure

215
Q

Stage C

A

patients with structural heart disease with prior or current symptoms of heart disease

216
Q

Stage D

A

patients with refractory heart failure (symptoms at rest despite maximal medical therapy) requiring specialized intervention

217
Q

heart failure pathophysiology

A

three main adaptive/injury response mechanisms

  • Frank Starling mechanism: increased preload via fluid retention “should” increase contractile force
  • Neurohumoral adaptation (RAAS activation, SNS stimulation):

-Dilation/hypertrophy/structural alterations:
-remodeling
-cardiac overload leads to ventricular hypertrophy leads to ischemic vulnerability leads to cell death by apoptosis
OR
-cardiac weakening leads to dilation and wall thinning leads to cell death by apoptosis leads to replacement with fibrotic tissue

218
Q

problem with compensatory mechanisms in HF

A

constant bombardment of sympathetic stimulation plus increased preload, afterload further stress the already weakened heart

219
Q

fluid retention in HF leads to

A

increased ventricular filling and ventricular dilation

220
Q

increased cardiac sympathetic (B-adrenergic) activity in HF leads to

A

increased oxygen demand and remodeling

221
Q

increased vascular sympathetic (a-adrenergic) activity in HF leads to

A

afterload increases

222
Q

RAAS activation in HF leads to

A

constriction, fluid retention, increased afterload and preload and remodeling

223
Q

vasopressin activation in HF leads to

A

constriction, fluid retention, increased afterload and preload

224
Q

ANP and BNP in HF leads to

A

early compensation that may fail later

vasodilation and decreased renin

225
Q

injury process to myocardium in HF leads to

A

inflammation and fibrosis

226
Q

compensatory responses in HF

A
  1. cardiac dilation
  2. activation of the sympathetic nervous system
  3. activation of the RAAS system
  4. retention of water and increased blood volume
227
Q

clinical manifestations of increased left ventricular pressure

A

higher L atrial pressure backing into pulmonary veins and capillaries (really bad - normally low pressure)

S/Sx: SOB, DOE, orthopnea, paroxysmal nocturnal dyspnea, cyanosis, basilar crackles

228
Q

inadequate systemic perfusion S/Sx

A

hypoxia, decreased capillary refill, fatigue, activation of RAAS, peripheral cyanosis/coolness

229
Q

forward effects of LV failure

A

systemic perfusion (in direction of blood flow

fatigue
oliguria
increased HR
faint pulses
restlessness
confusion
anxiety
230
Q

backward effects of LV failure

A

opposite of blood flow (increasing pressure backwards)

towards the right side of the heart

LV failure most common cause of RV failure because R side of heart not built to deal with high pressure

231
Q

clinical manifestations of increased RV pressure

A

increased pressure in R atrium, IVC/SVC

S/Sx: peripheral edema, venous congestion (enlarged liver), jugular venous distension

232
Q

backward effects of RV failure

A 
hepatomegaly
ascites: fluid in periotoneal cavity
splenomegaly
anorexia
subcutaneous edema
jugular vein distension
233
Q

clinical manifestations of HF

A

fatigue, exercise intolerance due to lack of adequate SV/CO

SOB: pulmonary congestions (lungs stretch and fill with greater volume/pressure to provide adequate pressure to fill heart)

systemic circulation congestions: dependent edema and JVD (liver distention later and GI discomfort increase)

234
Q

severe decompensation and pulmonary edema

A

alveolar capillaries have higher and higher pressures - leak into interstitium

eventually leak into alveolar lumen (sense of drowning because inadequate gas exchange)

hypoxia: patient cannot lie down at all

235
Q

HF sequelae

A

A.Fib and other arrhythmias

inflammation, fibrosis of myocardial cells

liver/kidney disease

lung disease/pulmonary hypertension

236
Q

hemostasis

A

arrest of bleeding: explosive, positive-feedback interaction of:
platelets
clotting factors
endothelial cells: lining all blood vessels (normally inhibits clotting)

under normal, healthy conditions, clotting is a localized phenomenon

237
Q

stages of clot formation and resolution

A
  1. vasoconstriction: reducing blood flow and limiting site of clot formation
  2. primary hemostasis: release substances to call other substances to site of injury (platelets can secrete and receive substances - recruitment and aggregation)
  3. secondary hemostasis: release of tissue factor, fibrin net formation - hold clot together
  4. antithrombotic conterregulation: resolution of clot where fibrinolysis causes stoppage of clot formation
238
Q

platelets

A

from megakaryocytes of bone marrow

5-10 day lifespan

platelet adhesion normally inhibited by prostacyclin (PGI2 from arachidonic acid) produced by intact endothelial cells

activation occurs rapidly on exposure to collagen via von Willebrand factor, ADP, thrombin

activated platelets release granules containing mediators that promote and amplify platelet aggregation

platelet conformation change on activation enhances aggregation: round to spiky (for more attachment sites)

239
Q

platelet receptors

A 
ADP
VWF
TxA2
Fibrinogen
Collagen
Epi
Thrombin
240
Q

platelet pro-clotting substances

A 
Factor V and VIII
VWF
ADP
TxA2
Thrombospondin
Fibrinogen
Fibronectin
241
Q

implication for platelet not having nucleus

A

no transcripxn

can’t make proteins (why aspirin is irreversible inhibitor of COX-1 because platelet can’t make new COX proteins

242
Q

VWF

A

von Willebrand Factor

connects/links platelet to subendothelial collagen that is exposed on damaged endothelium

243
Q

GpIb

A

Glycoprotein Ib

platelet surface membrane glycoprotein that acts as receptor for VWF. Without GpIb (and VWF), platelets cannot adhere to exposed collagen

244
Q

Fibrinogen

A

permits connecting/linking of adjoining platelets (and formation of stable clot)

245
Q

GPIIb/IIIa

A

Glycoprotein IIb/IIIa

integrin complex found on platelets. receptor for fibrinogen. without GpIIb/IIIa, platelet aggregation is inhibited

246
Q

Thromboxane A2 and ADP

A

potent promoters of platelet aggregation. TXA2 also stimulates expression of GpIIb/IIIa receptors

247
Q

serotonin in platelets

A

taken up from plasma by SERT (SERotonin Transport) and stored

released when platelets activated

role not completely understood: contributes to reflex vasoconstriction and enhances platelet ability to aggregate

controversial whether SSRIs used for depression increase bleeding risk

248
Q

platelet activation and aggregation steps

A
  1. endothelial cells normally prevent platelet aggregation by releasing NO and PGI2
  2. Injury to vessel wall exposes collagen and VWF which adhere and become activated
  3. activated platelets release chemical mediators to bind to and stimulate other platelets. aggregate by binding fibrinogen to GpIIb/IIIa receptors
249
Q

COX in platelet aggregation

A

activates prostacyclin from endothelium and thromboxane from platelets

250
Q

intrinsic pathway

A

less common

activated when factor XII contacts subendothelial substances exposed by vasular injury

251
Q

extrinsic pathway

A

most common

activated when tissue factor (TF - Factor III) released by damaged endothelial and tissue cells.

exposure of TF allows TF to form complex with factor VII in presence of calcium

factor VII activated to factor VIIa

252
Q

proteases in clotting cascade

A

active enzymes

XII, XI, IX (intrinsic), VIII (extrinsic)

X (common pathway - thrombin activator), II (thrombin)

IX, X, VIII and II require Vitamin K-dependent modification for full activity

253
Q

cofactors in clotting cascade

A

accelerators of proteases

V, VIII

254
Q

regulatory proteins in clotting cascade

A

Protein C, S, others

activated C splits/inactivates V and VIII, slowing clotting

255
Q

what is clot made of?

A

fibrin

product of fibrinogen after cleavage by thrombin (IIa)

clotting fxn doesn’t work well in liver disease

256
Q

prothrombin converting complex

A

Xa + Va + calcium + phospholipids

257
Q

key roles of thrombin in clotting

A
  • catalyzes conversion of fibrinogen into fibrin
  • activates XIII, which cause fibrin threads to crosslink
  • catalyzes conversion of V to Va
  • catalyzes VIII to VIIIa

-platelet activation

258
Q

conversion of fibrinogen into fibrin

A

fibrinogen = large soluble protein

fibrin = insoluble molecules that adhere to each other and assemble long fibrin threads (fibrils)

fibrils: entangle platelets and build up a spongy mass that gradually hardens

259
Q

antithrombin III

A

blocks thrombin and Xa

260
Q

protein C activation

A

protein C inactivates V and VIII, which accelerate protease activity

inactivation of V more physiologically important because V activates thrombin

261
Q

fibrinolysis

A

plasmin system breaks down clots when they are no longer needed

XII, HMWK, kallikrein, thrombin release plasminogen activators which cleave plasminogen to form plasmin

plasmin digests fibrin and fibrinogen and inactives V and VIII

262
Q

HMWK

A

high molecular weight kininogen

263
Q

fibrin split products

A

result of cleaved fibrin proteins (can be measured in lab tests)

264
Q

lab assessment of clotting fxn

A
  • platelet count
  • prothrombin time (PT) - international normalized ratio (INR)
  • activated partial thromboplastin time (aPPT)
  • d-dimer (fibrin degradation product created by breakdown of cross-linked fibrin due to plasmin activity)
265
Q

prothrombin time

A

PT

evaluates extrinsic pathway

266
Q

partial thromboplastin time

A

aPTT

evaluates intrinsic pathway

267
Q

balance of hemostasis

A

between:

pro-clotting forces (exposed collagen, VWF, platelets, clotting cascade proteins)

anti-clotting forces (intact endothelium, NO and prostacyclin, protein C to inactivate factor V, plasmin to break down clots, other proteins)

268
Q

principles of clotting and bleeding disorders

A
  • clotting needs to be limited to sites of injury, not disseminated thru body
  • clotting needs to be freely available and efficient at all times, to prevent blood loss in event of trauma
  • there needs to be a mechanism to STOP clotting when it is no longer needed
  • pathophysiology can lead to hypocoagulable or hypercoagulable states
269
Q

hypocoagulable states (bleeding disorders)

A
  • platelet deficiencies
  • deficiencies of clotting factors or cofactors
  • anti-clotting factor excesses

examples:

  • Von Willebrand disease (abnormal platelet adhesion and decreased VIII)
  • hemophilia (decreased VIII or IX)
  • heparin-induced thrombocytopenia (HIT): antibodies form to complexes of platelet factor IV and heparin
  • late DIC
270
Q

thromboytopenia

A

platelet deficiency

271
Q

ecchymoses

A

blotchy areas of hemorrhage (medium-sized)

272
Q

petechia

A

small blotchy areas of hemorrhage

273
Q

purpura

A

large blotchy areas of hemorrhage

274
Q

hypercoagulable states (clotting disorders)

A
  • deficient or abnormal anti-clotting factors
  • excessive pro-clotting factors

most common disorders:

  • factor V Leiden (genetic): AKA activated protein C resistance
  • prothrombin excess
  • early DIC: excess tissue factor-like substances promote disseminated clot formation in small vessels throughout body
275
Q

Disseminated Intravascular Coagulation (DIC)

A

tiny cloths (microthrombi and microemboli) form so clotting factors are used up and the person then has excessive bleeding and hemorrhagic shock

276
Q

where do clots come from in the absence of trauma/tissue injury with bleeding?

A

intrinsic pathway

Virchow’s Triad

277
Q

Virchow’s Triad

A

blood stasis - absence of normal flow along endothelium

damaged endothelium

hypercoagulability

278
Q

thrombus

A

clot

279
Q

embolus

A

traveling clot

280
Q

most common site of venous thromboembolism

A

deep veins of calf

281
Q

risk factors of venous thromboembolism

A

immobility/inflammation; decreased bloodflow

  • fracture
  • hip/knee replacement
  • major trauma
  • spinal cord injury
  • major general surgery
  • cancer
  • oral contraceptives and smoking
  • pregnancy
  • chemo
  • stroke w/ paralysis
  • arthroscopic knee surgery
  • central venous lines
  • CHF or RF
  • previous VTE
  • prolonged sitting
282
Q

DVT

A

clinical manifestation of thromboses

  • asymptomatic OR
  • leg pain, tenderness, swelling
  • discolored, cyanotic, venous distension distal
283
Q

PE

A

clinical manifestation of thromboses

  • tachypnea, dyspnea, pleuritic chest pain
  • may have cough, hemoptysis, leg pain
  • if massive, rapid death
  • up to 2/3 diagnosed at autopsy
284
Q

organ dysfxn w/ thrombus/embolism

A

depends on location

285
Q

lung dysfxn with thrombus

A

PE, lack of blood flow to all or part of one lungs leads to rapid loss of oxygen saturation.

large embolism can lead to death

286
Q

heart dysfxn w. thrombrus

A

acute coronary syndrome

myocardial infarction

287
Q

brain dysfxn w/ thrombus

A

stroke or transient ischemic attack (TIA)

288
Q

limb dyxfxn w/ thrombus

A

ischemia, gangrene

289
Q

kidney dysfxn w/ thrombrus

A

acute renal failure

290
Q

A. fib as major cause of stroke

A

disorganized rhythm causes blood stasis which sets up conditions for formation of thrombus

if it embolizes, it can enter systemic circulation and cause a stroke

291
Q

coronary blood flow overview

A

heart muscle uses abundant ATP for contraxn and ionic balance (Na/K); constantly generating action potentials

heart is .3% body weight but 7% oxygen utilization

90% coronary blood flow occurs during diastole

292
Q

part of the myocardium most vulnerable to ischemia

A

innermost, closest to endocardium

293
Q

myocardial arterial oxygen extraction

A

75% at rest

myocardium extracts 3 of 4 oxygen molecules from hemoglobin

294
Q

exercise increases oxygen demand

A

can only be met by increasing blood flow via vasodilation

stiff, narrowed vessels such as in CAD can’t respond to increased demand which leads to imbalance in cardiac oxygen supply and demand

295
Q

coronary occlusion

A

blockage of coronary artery almost always due to thrombus formation at site of an atherosclerotic plaque causing hypoxia and ischemia

296
Q

angina pectoris

A

chest pain

  • dull pressure pain at center of chest or substernal
  • may radiate to jaw, neck or arm
  • often brought on by exertion
  • atypical presentations common:
    • SOB, dizziness, pressure in upper back, fatigue, nausea (women)
297
Q

stable angina

A

effort-associated, usually relieved with rest and/or nitroglycerin

298
Q

unstable angina

A

unpredictable, can occur at rest or during sleep, may last longer than stable form

299
Q

prinzmetal’s variant angina

A

unpredictable, caused by coronary artery vasospasm

300
Q

Non-ST elevation myocardial infarction (NSTEMI)

A

partial thickness cardiac muscle infarct. usually occurs by developing a partial occlusion of a major coronary artery or a complete occlusion or a minor coronary artery

301
Q

ST elevation myocardial infarction (STEMI)

A

full thickness cardiac muscle infarct (transmural infarct). occurs because of total occlusion of major coronary artery

302
Q

myocardial infarction

A

disruption of flow in coronary vessel for >20 min resulting in permanent cell death

may have ST segment elevation (STEMI) or not (NSTEMI). both types will have elevated cardiac biomarkers due to necrosis of cells (troponins, CK-MB, myoglobin)

stable and unstable angina will NOT have biomarkers

303
Q

acute coronary syndrome

A

STEMI + biomarkers
NSTEMI + biomarkers
unstable angina (-biomarkers)

304
Q

STEMI

A

indicated by changes in ECG due to inability of cardiomyocytes to maintain their normal resting membrane potential and action potential activity. indicates full thickness infarct

typical ECG findings:
ST-segment elevation with pathological Q-wave formation. T-wave inversion possible but less-specific

305
Q

ST segment elevation indicates

A

full thickness cardiac muscle injury

306
Q

pathological Q-wave indicates

A

muscle necrosis

307
Q

T-wave inversion indicates

A

muscle ischemia

308
Q

normal ECG

A

isoelectric line before P wave: all atrial and ventricular cells at RMP

P-R segment: atrial cells in plateau phase; ventricular cells are at RMP

S-T segment: all ventricular cells in plateau phase, RMP approximately zero

309
Q

ST segment elevation in STEMI

A

as MI evolves, some cells become infarcted w. no electrical activity. ischemic cells still generate some.

ischemic cells have limited ATP to power membrane pumps and leak ions across cell membranes, which causes current flow even when heart is at rest

variation in electrical activity manifests as elevated ST

usually resolves over time

310
Q

clinical manifestations of MI

A 
chest pain
crushing pain radiating
indigestion/heartburn
nausea
severe fatigue
diaphoresis
blood pressure alterations, hypertension, hypotension
nerve dysfxn in diabetes
silent MI in diabetes
varied symptoms in women
loss of consciousness
311
Q

organ and cellular dysfxn in MI

A

disruption of large atherosclertoci plague within vessel sometimes associated with systemic inflammation

exposure of subendothelial plaque allows rapid platelet adhesion and activation, thromboplastin-like substances converting prothrombin to thrombin to accelerate coagulation

clot forms, rapidly expands, completely/partially occludes vessel

312
Q

development of atherosclerosis

A
  1. chronic endothelial injury leads to…
  2. endothelial dysfxn, permeability, and inflammation
  3. activated monocytes infiltrate arterial wall and smooth muscle proliferates
  4. macrophages engulf lipid to become foam cells
  5. lipid core forms in arterial wall and fibrous cap evolves
313
Q

endothelial injury

A

endothelium damaged by smoking, hypertension, hyperlipidemia, toxins, other damage. arterial bifurcations are particularly vulnerable to damage

314
Q

lipoprotein deposition

A

when endothelium is injured or disrupted, LDL molecules can migrate into arterial intima, where they are then modified by oxidation. modified LDL is proinflammatory and ingested by macrophages, creating foam cells causing a fatty streak in arterial wall

315
Q

inflammatory reaction

A

modified LDL, plus endothelial injury, attracts more inflammatory cells into arterial intima

316
Q

lipid core formation

A

lipids and cellular debris accumulate in vessel wall

317
Q

smooth muscle cell cap formation

A

smooth muscle cells stimulated by activated macrophages and foam cells, proliferate and migrate to surface of the plaque creating a fibrous cap over lipid core

when cap is thick, plaque stable. when cap is thin, more prone to thrombosis

318
Q

unstable plaque characteristics

A 
large lipid core
thin fibrous cap
inflammatory cells
macrophages
few smooth muscle cells
319
Q

percutaneous coronary intervention

A

mechanical revascularization, angioplasty

plain or drug-eluting stent placed to maintain vessel patency

320
Q

CABG

A

internal mammary artery graft bypasses occlusion and resupplies myocardium with blood flow

321
Q

pump function in MI

A

systolic dysfxn and diastolic dysfxn

leads to: varying degrees of acute impairment of cardiac output

sympathetic stimulation increases myocardial oxygen demand, creating a vicious cycle

322
Q

structural complications of MI

A

ventricular septal rupture

mitral regurgitation

aneurysm

cardiogenic shock

invasive hemodynamic monitoring needed

increased risk of second MI until scar forms

323
Q

electrical complications of MI

A

ventricular arrhythmia

areas of myocardial ischemia and death

eleated sympathetic tone

initially all cells still electrically coupled
-increased intracellular Ca closes some gap jxns which stops spread of depolarization but predispose to reentry arrhythmias and ventricular fibrillation (ultimately scarring takes over reducing ventricular ectopy)

324
Q

ectopy

A

irregular heart beat NOT coming from SA node (pretty much anywhere else)

325
Q

functional complications of MI

A

myocardial stunning - persistent systolic dysfxn for several weeks after MI revascularization

myocardial hibernation - prolonged reduction in systolic fxn due to coronary artery insufficiency

MI is risk factor for HF: acute or gradual

326
Q

anti-ischemic therapy in NSTEMI/unstable angina

A

oxygen
vasodilators
B-blockers
morphine PRN

327
Q

anti-platelet therapy in NSTEMI/unstable angina

A

antiplatelet agents

anticoagulants

328
Q

STEMI: acute management therapeutic approach

A

restore blood flow

reduce cardiac oxygen demand/increase oxygen supply

reduce workload of heart

reduce pain (reduce sympathetic nervous system response)

limit ventricular remodeling

329
Q

restoring blood flow in STEMI

A

PCI (+ aspiring + clopidogrel)

lyse existing clot (TPA + aspirin + clopidogrel)

330
Q

reducing cardiac oxygen demand/increase oxygen supply in STEMI

A

B-blockers
oxygen
morphine
nitroglycerin

331
Q

reducing pain in STEMI

A

morphine (also venodilates to reduce preload and modest arterial dilation, to reduce afterload)

332
Q

limiting ventricular remodeling in STEMI

A

ACE inhibitor

333
Q

drug eluting stents

A

restenosis after stenting can occur because smooth muscle cell proliferation and migration that re-occludes vessel

prevented with stent that elutes anti-proliferative drug over weeks/months

re-endothelialization is reduced and can increase risk of late thrombosis (concurrent use of aspirin and clopidogrel)

334
Q

why is PCI preferred to fibrinolysis?

A

better at reducing overall short-term death, non-fatal reinfarction, stroke, and combined endpoint of death, non-fatal reinfarction, and stroke

better followup

335
Q

nitroglycerin in acute STEMI

A

does not reduce mortality

sublingually every 5 min x 3 doses

can be given IV, slow and continuous

glass bottle, special tubing

NOT given with PDE5 inhibitors

336
Q

early initiation of maintenance therapy to prevent reoccurrence

A

treatment of hyperlipidemia, HTN, diabetes

clopidogrel, aspirin

beta-blockers

ACEI/ARBs

Pathophysiology, Pharmacology, and Therapeutics (7 decks)

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