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Flashcards in Physio 2 USMLE Deck (330):
1

Tidal volume

Volume of air that enters and leaves the lung in a single cycle. 500ml

2

Functional residual capacity

Amount of air in the lungs after passive expiration. 2,700ml

3

Inspiratory capacity

Maximal volume of gas inspired from FRC. 4,000ml

4

Inspiratory reserve volume

Air that can be inhaled after normal inspiration. 3,500ml

5

Expiratory reserve volume

Air that can be expired after a normal expiration. 1,500ml

6

Residual volume

Air in the lungs after maximal expiration. 1,200ml

7

Vital capacity

Maximal air that can expired after maximal inspiration. 5,500ml

8

Total lung capacity

Air in the lungs after maximal inspiration. 6,700ml

9

Total ventilation

Total ventilation = Tidal volume X respiratory rate.

10

Dead space

Regions that contain air but do not exchange O2 and CO2

11

Anatomic dead space

Conducting zones. Approximately equal to person't weight in pounds.

12

Alveolar dead space

Alveoli with air but without blood flow

13

Physiologic dead space

Anatomic dead space plus alveolar dead space

14

Alveolar ventilation

Tidal volume - anatomic dead space X respiratory rate.

15

Lung recoil

Force that collapses the lung. As the lung enlarges, recoil increases and vice versa.

16

Intrapleural pressure

Normally -5 cmH2O. Force that expands the lung. The more negative, the more lung expansion.

17

Lung mechanics before inspiration

Glotis is open but no air is flowing - alveolar pressure = 0. Intrapleural pressure and lung recoil are equal but opposite. Gravity increases intrapleural pressure at the apex and decreases it at the bases. Apex alveoli are more distended.

18

Lung mechanics during inspiration

Diaphragm contracts, intrapleural pressure becomes more negative. Expansion of alveoli makes alveolar pressure negative causing air to flow into the lungs.

19

Lung mechanics at the end of inspiration

Intrapleural pressure and recoil are the same but opposite. Alveolar pressure returns to zero and air stops flowing in.

20

Lung mechanics during expiration

Diaphragm relaxes, intrapleural pressure increases, lung recoil collpases the lung. Alveoli compress the air and alveolar pressure becomes positive and air flows out of the lungs until alveolar pressure is back to zero. Lung recoil and intrapleural pressure become equal but opposite.

21

Assisted control mode ventilation

Inspiration is initiated by the patient or the machine if no signal is detected.

22

Positive end-expiratory pressure

Does not allow intraalveolar pressure to return to zero at the end of expiration. The larger lung volume prevents atelectasis.

23

What is lung compliance?

It's the change in volume with a change in pressure. Increased compliance means more air flows in with a given change in pressure. Decreased compliance means the opposite. The steeper the slope of the lung inflation curve, the greater the compliance. Emphysema = very compliant; fibrosis = not compliant.

24

Components of lung recoil

1) the tissue's collagen and elastin fibers and 2) the surface tension (greatest component)

25

Functions of surfactant

Lowers lung recoil and increases compliance (↓ surface tension) more in small alveoli than large alveoli; reduces capillary filtration forces reducing tendency to develop edema.

26

Pathophysiology of respiratory distress syndrome

Low surfactant --> ↑ recoil, ↓ compliance (a greater change in intrapleural pressure is necessary to inflate the lungs); alveoli collapse (atelectasis); more negative intrapleural pressures promote capillary filtration (pulmonary edema)

27

Airway resistance

R = 1/r4; first and second bronchi have less radius than alveoli, therefore more resistance. Ach increases resistance (bronchoconstriction), catecholamines decrease resistance (bronchodilation)

28

Effect of lung volume on airway resistance

↑ lung volume --> ↑ radius --> ↓ resistance. The more negative the intrapleural pressure, the less resistance

29

Lung volumes in obstructive disease

↑ TLC, ↑ RV, ↑ FRC, ↓ FEV1, ↓ FVC, ↓ FEV1/FVC

30

Lung volumes in restrictive disease

↓ TLC, ↓ RV, ↓ FRC, ↓ FEV1, ↓ FEV, ↑ FEV1/FVC

31

Pressure of alveolar O2 and CO2

PAO2 = 100mmHg; PACO2 = 40mmHg

32

Pressure of venous pulmonary capillary O2 and CO2

PvO2 = 40mmHg; PvCO2 = 47mmHg

33

Pressure of arterial pulmonary capillary O2 and CO2

PO2 = 100mmHg; PCO2 = 40mmHg

34

Which factors affect PCO2?

Metabolic CO2 production and alveolar ventilation

35

Relationship between alveolar ventilation and PACO2

Inversely proportional. Hyperventilation decreases PACO2; hypoventilation increases PACO2.

36

Relationship between PAO2 and PACO2

↓ PACO2 --> ↑ PAO2 (hyperventilation); ↑ PACO2 --> ↓ PAO2 (hypoventilation)

37

Which factors affect PAO2?

Atmospheric pressure, oxygen concentration of inspired air and PACO2

38

What determines oxygen content?

Hemoglobin concentration. 1.34ml O2 combines with each gram of hemoglobin.

39

Amount of dissolved oxygen in the blood

0.3 volumes %; 0.3ml per 100ml of blood. Determines PO2 which acts to keep oxygen bound to Hb

40

What determines oxygen attachment to hemoglobin?

PO2 and the affinity of the individual attachment sites. The higher the affinity, the less PO2 is needed to keep it attached

41

What determines PO2?

Amount of oxygen dissolved in plasma. Normally 0.3 volumes %.

42

Site 4 of hemoglobin

Oxygen is attached at 100mmHg. Least affinity, last site to be saturated.

43

Site 3 of hemoglobin

Oxygen is attached at 40mmHg. More affinity than site 4, less affinity than site 2.

44

Site 2 of hemoglobin

Oxygen is attached at 26mmHg which is p50. More affinity, second site to be saturated.

45

Site 1 of hemoglobin

Oxygen remains attached under physiologic conditions. Highest affinity, first site to be saturated.

46

Factors that shift oxygen dissociation curve to the right

↑ CO2, ↑ 2,3BPG, fever, acidosis

47

Factors that shift oxygen dissociation curve to the left

↓ CO2, ↓ 2,3BPG, hypothermia, alkalosis, HbF, methemoglobin, carbon monoxide, stored blood

48

How is CO2 carried in the blood?

5% dissolved; 5% attached to Hb (carbamino compounds); 90% as bicarbonate.

49

Main drive for ventilation

H+ ions from dissociated H2CO3 which stimulate central chemoreceptors. H2CO3 is proportional to PCO2 of CSF

50

Central chemoreceptors

Sense [H+] which is proportional to PCO2 and H2CO3 of the CSF (not systemic)

51

Peripheral chemoreceptors

Carotid bodies (afferents via IX), aortic bodies (afferents via X). Monitor PO2 and [H+/CO2]

52

Main drive for ventilation in severe hypoxemia

Peripheral chemoreceptors sense PaO2 (dissolved oxygen) once PaO2 falls to 50-60mmHg.

53

Ventilatory response to chronic hypoventilation

Peripheral chemoreceptors are the main drive for ventilation eventhough PaCO2 is increased.

54

Ventilatory response to anemia

PaO2 and PACO2 are normal, therefore neither peripheral nor central chemoreceptors respond.

55

Central control of ventilation

Apneustic center in the caudal pons promotes prolonged inspiration. Pneumotaxic center in the rostral pons inhibits apneustic center. Efferents are from the medulla to the phrenic nerve (C1-C3) to the diaphragm

56

Differences in ventilation between the base and the apex of the lung

Base intrapleural pressure is -2.5, alveoli are compliant and small with a small volume of air but receive a large amount of ventilation; Apex pressure is -10, alveoli are large and stiff and contain a large volume of air but receive small amount of ventilation.

57

Differences in blood flow between the base and the apex of the lung

Blood vessels of the apex are less distended, have more resistance and receive less blood flow. Blood vessels of the base are more distended, have less resistance and receive more blood flow

58

Ventilation/perfussion relationship at the base of the lungs

Blood flow is higher than ventilation, the relationship is less than 0.8; the bases are underventilated, ↑ shunts

59

Ventilation/perfusion relationship at the apex of the lungs

Blood flow is lower than ventilation, the relationship is more than 0.8; the apex are overventilated, ↑ dead space

60

What does a ventilation/perfussion relationship under and over 0.8 mean?

Under 0.8 (at the bases) lungs are underventilated and less gas exchange takes place, therefore PACO2 and end-capillary PCO2 will be higher and PAO2 and end-capillary PO2 will be lower.

61

What is hypoxic vasoconstriction?

A decrease in PAO2 causes vasoconstriction and shunting of blood through that segment.

62

What is the effect of a thrombus in a pulmonary artery?

Blood flow decreases, therefore ↑ Va/Q --> ↓ PACO2, ↑ PAO2

63

What is the effect of a foreign object occluding a terminal bronchi?

Ventilation decreases, therefore ↓ Va/Q --> ↑ PACO2, ↓ PAO2

64

What constitutes a pulmonary shunt?

Regions of the lung where blood is not ventilated. Low Va/Q relationship.

65

What constitutes alveolar dead space?

Regions of the lung where there's no blood flow in spite of ventilation. High Va/Q relantionship

66

Va/Q > 0.8

Represents alveolar dead space. Can be reversed with supplemental O2

67

Va/Q < 0.8

Represents a pulmonary shunt. Cannot be reversed with supplemental O2

68

What is the normal A-a gradient?

5-10 mmHg

69

Hypoventilation

↓ PAO2 but diffusion and A-a gradient are normal. Perfusion-limited defect.

70

What is a perfusion-limited defect?

There's a lung problem but A-a gradient is normal

71

What is a diffusion-limited defect?

There's a lung problem where A-a gradient is below normal, therefore diffusion isn't normal

72

Diffusion impairment lung defect

Due to structural problem (↑ thickness or ↓ surface area). A-a gradient is more than normal. Supplemental oxygen compensates structural deficit but increased A-a gradient remains. Fibrosis, emphysema.

73

Diffusion capacity of the lung

Its measured with CO because it's a diffusion-limited gas. Structural problems decrease CO uptake. It's an index of surface area and membrane thickness.

74

Pulmonary right-left shunt

↓ Va/Q. There is an increased A-a gradient that is unresponsive to supplemental O2. Atelectasis or ARDS.

75

PO2 in atrial septal defect

↑ Right atrial PO2, ↑ right ventricular PO2, ↑ pulmonary artery PO2, ↑ pulmonary blood flow and pressure

76

PO2 in ventricular septal defect

No change in right atrial PO2, ↑ right ventricular PO2, ↑ pulmonary artery PO2, ↑ pulmonary flow and pressure

77

PO2 in patent ductus arteriosus

No change in right atrial PO2 nor right ventricular PO2, ↑ pulmonary artery PO2, ↑ pulmonary flow and pressure

78

Effect of sympathetic stimulation in the GI tract

↓ motility, ↓ secretions, ↑ contraction of sphincters

79

Effect of parasympathetic stimulation in GI tract

↑ motility, ↑ secretions, ↑ relaxation of sphincters (except LES which contracts), ↑ gastrin release

80

Hormones of the GI system

Gastrin, CCK, secretin, GIP

81

Stimulus for gastrin secretion

Stomach distension. Stomach acid in the duodenum inhibits gastrin release

82

Sources of gastrin

G cells of the stomach, antrum, duodenum

83

Actions of gastrin

Stimulates acid secretion by parietal cells, increases motility and secretions.

84

Source of secretin

S cells of the duodenum

85

Stimulus for secretin release

Acid entering the duodenum

86

Actions of secretin

Stimulates HCO3 secretion by pancreas to neutralize acid entering duodenum

87

Source of CCK

Cells lining the duodenum

88

Stimulus for CCK secretion

Fat and amino acids entering duodenum

89

Actions of CCK

Inhibits gastric emptying, stimulates pancreatic enzyme secretion, stimulates contraction of the gallbladder and relaxation of sphincter of Oddi.

90

Source of GIP

Duodenum

91

Stimulus for GIP secretion

Fat, carbs and amino acids

92

Actions of GIP

Inhibits stomach motility and secretion

93

Properties of GI smooth muscle

Stretch stimulates contraction, electrical syncytium with gap junctions, pacemaker activity

94

Factors that inhibit gastric motility

Acid in the duodenum (secretin), fat in the duodenum (CCK), hypoerosmolarity in duodenum, distension of duodenum

95

Factors that stimulate gastric motility

Distension of the stomach and ACh

96

What are the different contractions of the intestines?

Segmentation contractions (mixing), peristaltic movements (propulsive).

97

What factors control the ileocecal sphincter?

Distension of the ileum relaxes, distension of the colon contracts

98

What are the different contractions of the colon

Segmentation contractions (haustrations), peristalsis and mass movements

99

Composition of salivary secretions

Low in NaCl because of reabsorption; High in K and HCO3 because of secretion; alpha-amylase begins digestion of carbs; fluid is hypotonic due to NaCl reabsorption and impermeability of ducts to water

100

Parietal cells

Located in the middle part of the gastric glands. Secrete HCl and intrinsic factor.

101

Chief cells

Located in the deep part of the gastric glands. Secrete pepsinogen which is converted to pepsin by acid medium. Pepsin begins digestion of proteins to peptides

102

Mucous cells of the stomach

Located in the superficial part if the gastric glands (gastric pits). Secrete mucus and HCO3. Secreteion is stimulated by PGE2

103

Ionic composition of gastric secretions

High in H+, K+ and Cl-, low in Na+. Vomiting produces metabolic alkalosis and hypokalemia.

104

Control of acid secretion

Acetylcholine, histamine and gastrin stimulate parietal cells to secrete acid.

105

Secretion of acid by parietal cells

CO2 is extracted from the blood and combined into H2CO3 by carbonic anhydrase. H+ ions are exchanged by the proton pump for K+ ions (active antitransport)

106

Pancreatic amylase

Hydrolyzes α-1,4-glucoside bonds forming α-limit dextrins, maltotriose and maltose

107

Pancreatic lipase

Needs colipase which displaces bile from surface of micelles. Lipase digests triglycerides to two free fatty acids and one 2-monoglyceride

108

Cholesterol esterase

Hydrolizes cholesterol esters to yield cholesterol and free fatty acids

109

Pancreatic proteases

Trypsinogen is converted to trypsin by enterokinase --> chymotrypsinogen is converted to chymotrypsin by trypsin --> procarboxypeptidase is converted to carboxypeptidase by trypsin

110

Ionic composition of pancreatic secretions

Isotonic due to permeability of ducts to water and high in HCO3. Stimulated by CCK and secretin.

111

What are the primary bile acids?

Cholic acid and chenodeoxycolic acid. Synthesized in the liver from cholesterol.

112

How are bile salts formed?

Bile acids (cholic and deoxycholic) are conjugated with glycine and taurine which mix with cations to form salts.

113

What are the secondary bile acids?

Formed by deconjugation of bile salts by enteric bacteria - deoxycholic acid (from cholic acid) and lithocolic acid (from chenodeoxycholic acid). Lithocholic acid is hepatotoxic and is excreted.

114

Enterohepatic circulation

Bile acids are reabsorbed only in the distal ileum. Resection or malabsoption syndromes lead to steatorrhea and cholesterol gallstones.

115

What are the components of bile?

Conjugated bile acids (cholic and chenodeoxycholic), billirubin, lecithin and cholesterol.

116

How are carbohydrates absorbed?

Glucose and galactose via active secondary Na cotransporter. Fructose is absorbed independently

117

How are amino acids absorbed?

Secondary active transport linked to Na and receptor-mediated endocytosis.

118

How are lipids absorbed?

Micelles diffuse to the brush border then digested lipids (2-monoglycerides, fatty acids, cholesterol and ADEK vitamins) diffuse into enterocytes. Triglycerides are resynthesized and packaged as chylomicrons with apoB48. Leave the intestine via lymphatics to thoracic duct.

119

↑ glomerular pressure, ↓ peritulbuar pressure, ↓ RPF

Efferent arteriole constriction

120

↓ glomerular pressure, ↑ peritubular pressure, ↑ RPF

Efferent arteriole dilation

121

↓ glomerular pressure, ↓ peritulbuar pressure, ↓ RPF

Afferent arteriole constriction

122

↑ glomerular pressure, ↑ peritulbuar pressure, ↑ RPF

Afferent arteriole dilation

123

Afferent arteriole dilation

↑ glomerular pressure, ↑ peritulbuar pressure, ↑ RPF, ↑ GFR

124

Afferent arteriole constriction

↓ glomerular pressure, ↓ peritulbuar pressure, ↓ RPF, ↓ GFR

125

Efferent arteriole dilation

↓ glomerular pressure, ↑ peritubular pressure, ↑ RPF, ↓ GFR

126

Efferent arteriole constriction

↑ glomerular pressure, ↓ peritulbuar pressure, ↓ RPF, ↑ GFR, ↑ FF

127

Plasma oncotic pressure changes as blood flows through the nephron

Oncotic pressure increases because filtered fluid increases protein concentration. Oncotic pressure is resposible for peritubular reabsorption

128

Normal capillary hydrostatic pressure of the glomerulus

45 mmHg

129

Normal capillary oncotic pressure of the glomerulus

27 mmHg

130

Normal hydrostatic pressure of bowman's capsule

10 mmHg

131

Normal GFR value

120 ml/min

132

Normal RPF value

600 ml/min

133

Normal filtration fraction value

FF = GFR/RPF = 120mi/min / 600ml/min = 0.20

134

Effect of sympathetic stimulation in the nephron

↓ GFR, ↑ FF, ↑ peritubular reabsoption

135

Effect of angiotensin II in the kidney

Vasoconstriction of the efferent arteriole more than afferent --> maintains GFR

136

Filtered load

Rate at which a substance filters into Bowman's capsule = FL = GFR x Free plasma concentration

137

Excretion of a substance in the urine

Excretion = filtered load + (amount secreted - amount reabsorbed) = filtered load + transport OR urine concentration X urine flow rate

138

Characteristics of a Tm system

Carriers become saturated, carriers have high affinity, low back leak. The filtered load is reabsorbed until carriers are saturated - the excess is excreted.

139

Renal treshold for glucose

180 mg/dl or 1.8 mg/ml. Represents the beginning of splay.

140

Tm rate of reabsorption of glucose

375 mg/min. Represents the maximum filtered load that can be reabsorbed when all carriers in the kidney are saturated (end of splay region).

141

Glucose reabsorption graph

At normal glucose levels, the amount filtered is the same as the amount reabsorbed. At treshold (beginning of splay), the excretion curve starts to ascend and the amount filtered exceeds the amount reabsorbed.

142

Substances that are reabsorbed using a Tm system

Glucose, amino acids, small peptides, myoglobin, ketones, calcium, phosphate.

143

Characteristics of a gradient-time system

Carriers are not saturated, carriers have low affinity, high back leak

144

Substances that are reabsorbed using a gradient-time system

Sodium, potassium, chloride and water

145

Substances secreted using a Tm system

PAH. 20% filtered, 80% secreted.

146

Graph for PAH secretion

At low plasma concentration secretion is 4 times the filtered load. When carriers become saturated, secretion reaches a plateau and the amount excreted is proportional to the amount filtered.

147

How is the net transport rate for a substance calculated?

Net transport rate = filtered load - excretion rate = (GFR X Px) - (Ux X V)

148

Effects of blood pressure changes in the kidney

GFR and RBF are maintained constant within the autoregulatory range. Urine flow is directly proportional to blood pressure due to pressure natriuresis and pressure diuresis.

149

What is clearance and how is it calculated?

It's the volume of plasma cleared of a substance over time. Clearance = excretion / Px = Ux X V / Px

150

Characteristics of glucose clearance

At normal glucose levels, clearance is zero. Above treshold levels, clearance increases as plasma concentration increases but never reaches GFR as there's always glucose reabsorption.

151

Characteristics of inulin clearance

A constant amount of inulin is cleared regardless of plasma concentration (parallel line to x axis). Inulin clearance is equal to GFR because it's not secreted nor reabsorbed. If GFR increases, clearance increases (line shifts upward), and vice versa.

152

Characteristics of creatinine clearance

A constant amount of creatinine is cleared regardless of plasma concentration, but creatinine clearance is more than GFR because some is always secreted.

153

Characterisics of PAH clearance

As plasma concentration increases, clearance decreases because carriers that mediate active secretion become saturated. At normal levels, PAH clearance = RPF because all is excreted.

154

How is GFR calculated using inulin?

GFR is equal to inulin clearance because it's only filtered and none is secreted nor reabsorbed. Cin = GFR = Uin X V / Pin

155

How is creatinine production calculated?

Creatinine production = creatinine excretion = filtered load of creatinine = [Cr]p X GFR. Creatinine is filtered and secreted, not reabsorbed.

156

How does inulin concentration change as it passes through the nephron?

Inulin becomes more concentrated as it passes through the tubules because water is being reabsorbed and not inulin.

157

Gold standard to measure GFR

Inulin clearance because it's filtered but not secreted nor reabsorbed.

158

Gold standard to measure RPF

PAH clearance because some is filtered and the remaining is all secreted.

159

How is effective RPF calculated?

PAH clearance = RPF = Upah X V / Ppah

160

How is renal blood flow calculated?

ERPF / 1-Hct; ERPF = Upah X V / Ppah

161

What does positive free water clearance mean?

Water is being eliminated. Hypotonic urine is being formed to increase plasma osmolarity.

162

What does negative free water clearance mean?

Water is being conserved. Hypertonic urine is being formed to lower plasma osmolarity.

163

How is free water clearance calculated?

V - (Uosm(V) / Posm)

164

Which substance is cleared the most: PAH, inulin, glucose, creatinine

PAH

165

Which substances are cleared more than glucose?

Sodium, inulin, creatinine, PAH

166

Which substance is cleared the least: PAH, inulin, glucose, creatinine

Glucose

167

Which substances are cleared more than inulin?

Creatinine, PAH

168

Which substances are cleared less than creatinine?

Inulin, glucose, sodium

169

Transporters in the luminal membrane of the proximal tubule

Secondary Na/glucose cotransporter, secondary Na/amino acid cotransporter, secondary Na/H countertransporter

170

What substances are reabsorbed in the proximal tubule and how much?

Na (2/3 of filtered load), glucose (100%), amino acids (100%), HCO3 (indirectly, 80%), H20 (2/3), K (2/3), Cl (2/3)

171

Tubular osmolarity at beginning and end of proximal tubule

At the beginning and end is isotonic with plasma but only 1/3 of the filtered load.

172

Transporters in the basal membrane of proximal tubule

Na/K ATPase - luminal membrane secondary Na transporters depend on this.

173

Transporters in the basolateral membrane of proximal tubule

Na/K ATPase - luminal membrane secondary Na transporters depend on this.

174

Most energy-dependant process in the nephron

Active reabsorption of Na by the basal and basolateral Na/K ATPase

175

Characteristics of the loop of henle

Descending limb is permeable to water so water difuses out and intraluminal osmolarity increases to 1,200mOsm Ascending limb is impermeable to water and Na is actively pumped out by Na/K/2Cl pump so fluid becomes hypotonic. Flow is slow, anything that increases flow, decreases capacity to concentrate urine.

176

Characteristics of the collecting duct

Impermeable to water unless ADH is present. ADH increases permeability to H20 and urea to concentrate urine. Tight junctions with little back-leak.

177

Specialized cells of the distal tubule and collecting duct

Principal cells (aldosterone) and intercalated cells (create HCO3)

178

Actions of principal cells of the distal tubule and collecting duct

Aldosterone increases Na receptors in the membrane and increases primary transport by Na/K ATPase. Secondary transport of Na and secretion of K.

179

Actions of the distal tubule and collecting duct

Reabsorption of Na and secretion of K (stimulated by aldosterone), acidification of the urine (secretion of H and creation of HCO3)

180

Urine buffer systems

H2PO4- (dihydrogen phosphate) (tritratable acid) buffers 33% of secreted H. NH4+ (amonium) (nontritratable acid) buffers the remaining secreted H.

181

How is potassium affected by acidosis?

High concentration of ECF H --> H diffuses to ICF --> K diffuses to ECF --> hyperkalemia

182

How is potassium affected by alkalosis?

Low concentration of ECF H --> H diffuses to ECF --> K diffuses to ICF --> hypokalemia

183

Potassium dynamics in acute alkalosis

Hypokalemia, ↑ intracellular K, ↑ renal K excretion, negative K balance

184

Potassium dynamics in chronic alkalosis

Hypokalemia, ↓ intracellular K, ↑ renal K excretion, negative K balance

185

Potassium dynamics in acute acidosis

Hyperkalemia, ↓ intracellular K, ↓ renal K excretion, positive K balance

186

Potassium dynamics in chronic acidosis

Hyperkalemia, ↓ intracellular K, ↑ renal K excretion, negative K balance

187

How is potassium balance in acute acidosis?

Positive (potassium is reabsorbed)

188

How is potassium balance in acute alkalosis?

Negative (potassium is excreted)

189

How is potassium balance in chronic alkalosis?

Negative (potassium is excreted)

190

How is potassium balance in chronic acidosis?

Negative (potassium is excreted)

191

How is plasma potassium concentration in alkalosis?

Hypokalemia

192

How is plasma potassium concentration in acidosis?

Hyperkalemia

193

What is the difference in potassium dynamics between acute and chronic alkalosis?

Acute alkalosis --> ↑ intracellular K; Chronic alkalosis --> ↓ intrecellular K

194

What is the difference in potassium dynamics between acute and chronic acidosis?

Acute acidosis --> ↓ renal K excretion, positive K balance; Chronic acidosis --> ↑ renal K excretion, negative K balance

195

Changes in respiratory acidosis

Hypoventilation --> ↑ PaCO2 --> ↑ H and slight ↑ in HCO3 --> ↓ pH

196

Changes in respiratory alkalosis

Hyperventilation --> ↓ PaCO2 --> ↓ H and HCO3 --> ↑ pH

197

Changes in metabolic acidosis

Gain of H or loss of HCO3 --> ↓ HCO3 --> ↑ pH. To see if gain of H or loss of HCO3 check anion gap.

198

Changes in metabolic alkalosis

Loss of H or gain in HCO3 --> ↑ HCO3 --> ↑ pH. To see if gain of H or loss of HCO3 check anion gap.

199

Normal values of PCO2, HCO3 and pH

pH = 7.4; PCO2 = 40mmHg; HCO3 = 24mmol/L

200

↑pH, ↑ HCO3, ↑PCO2, ↓PO2, alkaline urine

Partially compensated metabolic alkalosis

201

↓pH, ↑PCO2, ↑HCO3, ↓PO2, acid urine

Partially compensated respiratory acidosis

202

↑pH, ↓PCO2, ↓HCO3, normal PO2, alkaline urine

Partially compensated respiratory alkalosis

203

↓pH, ↓PCO2, ↓HCO3, normal PO2, acid urine

Partially compensated metabolic acidosis

204

Normal plasma anion gap value

PAG = 12

205

Conditions that increase plasma anion gap

Lactic acidosis, ketoacidosis, ingestion of salicylate

206

Hyperchloremic non-anion gap metabolic acidosis

Loss of HCO3 (as in diarrhea) causes increased absorption of solutes and water, increasing Cl. Therefore ↓HCO3 and ↑Cl with a plasma anion gap of 12.

207

Factors that affect hormone binding protein synthesis

Estrogen increases binding proteins; androgens decrease binding proteins. In pregnancy there's increased total hormones with normal levels of free hormone.

208

Site of synthesis of CRH

Paraventricular nucleus

209

Site of synthesis of TRH

Paraventricular nucleus

210

Site of synthesis of PIF

Arcuate nucleus

211

Site of synthesis of GHRH

Arcuate nucleus

212

Site of synthesis of GnRH

Preoptic region

213

Site of synthesis of ADH

Supraoptic and paraventricular nuclei

214

How do hypothalamic hormones reach the anterior pituitary?

Hormones are released in the hypophyseal-portal system

215

Hypothalamic hormones

GHRH, GnRH, PIF (dopamine), TRH, CRH, Somatostatin, ADH, prolactin

216

Anterior pituitary hormones

ACTH, TSH, LH, FSH, GH, prolactin

217

Sheehan syndrome

Ischemic necrosis of the pituitary due to severe blood loss during delivery. Causes hypopituitarism.

218

Obstruction of pituitary stalk

Adenoma compresses pituitary stalk and decreases secretion of anterior pituitary hormones except prolactin.

219

What prevents downregulation of pituitary receptors?

Pulsatile release of hypothalamic hormones.

220

Hyperprolactinemia

Results from dopamine antagonists or pituitary adenomas that compress the pituitary stalk. Amenorrhea, galactorrhea, decreased libido, impotence, hypogonadism

221

What hormone controls release of cortisol and adrenal androgens?

ACTH

222

What hormone regulates release of aldosterone?

Angiotensin II and also potassium in hyperkalemia

223

Layers of the adrenal cortex

From external to internal: glomerulosa (aldosterone), fasciculata (cortisol), reticularis (androgens). "Salt, Sugar and Sex; the deeper it goes the sweeter it gets"

224

Consequences of loss of zona glomerulosa

No aldosterone: loss of Na, ↓ECF, ↓blood pressure, circulatory shock, death

225

Consequences of loss of zona reticularis

No cortisol: circulatory failure (cortisol is permissive for cathecolamine vasoconstriction), can't mobilize energy stores during exercise of cold (hypoglycemia)

226

Consequences of loss of adrenal medulla

No epinephrine: decreased capacity to mobilize fat and glycogen during stress. Not necessary for survival.

227

What are the 17-OH steroids?

17OHpregnenolone, 17OHprogesterone, 11-deoxycortisol, cortisol. Urinary 17OH steroids are an index of cortisol secretion.

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What is the rate-limiting enzyme for steroid hormone synthesis?

Desmolase - converts cholesterol into pregnenolone

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What are the 17-ketosteroids?

DHEA and androstenidione

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DHEA

Weak androgen 17-ketosteroid conjugated with sulfate to make it water-soluble

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What is measured as an index of androgen production?

Urinary 17-ketosteroids. In females and prepubertal males is an index of adrenal 17-ketosteroids. In postpubertal males is an index of 2/3 adrenal androgens and 1/3 testicular androgens.

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Stimulus for the zona glomerulosa

Angiotensin II and potassium in hypekalemia stimulate production of aldosterone

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Hormone responsible for negative feedback for ACTH release

Cortisol

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Enzyme deficiencies that produce congenital adrenal hyperplasia and low cortisol levels

21β-OH, 11β-OH and 17α-OH all result in low cortisol levels.

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21β-OH deficiency

No aldosterone: loss of Na, ↓ECF, ↓blood pressure in spite of high renin and angiotensin II, circulatory shock, death. No cortisol (low 17OH steroids): skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia, hypotension (persmissive for catecholamines), fasting hypoglycemia. Excess androgens (17-ketosteroids): female pseudohermaphrodite, hirsutism

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11β-OH deficiency

Excess 11-deoxycorticosterone: Na and water retention, low-renin hypertension. No cortisol (low 17OH steroids): skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia, fasting hypoglycemia. Excess androgens (17-ketosteroids): female pseudohermaphrodite, hirsutism

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17α-OH deficiency

Excess 11-deoxycorticosterone and low aldosterone (no AII): Na and water retention, low-renin hypertension. No cortisol: skin hyperpigmentation (due to excess ACTH), adrenal hyperplasia; corticosterone partially compensates low cortisol levels. No 17-ketosteroids: male pseudohermaphrodite, no testosterone, no estrogen.

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↓17OH-steroids ↑ACTH, ↓blood pressure, ↓mineralocorticoids, ↑17-ketosteroids

21β-OH deficiency

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↓17OH-steroids ↑ACTH, ↑blood pressure, ↓aldosterone, ↑11-deoxycorticosterone, ↑17-ketosteroids

11β-OH deficiency

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↓17OH-steroids ↑ACTH, ↑blood pressure, ↑ aldosterone, ↑11-deoxycorticosterone, ↓17-ketosteroids

17α-OH deficiency

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Stress hormones

GH, Glucagon, cortisol, epinephrine

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Actions of GH in stress situations

Mobilizes fatty acids by increasing lipolysis in adipose tissue

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Actions of glucagon in stress situations

Mobilizes glucose by increasing liver glycogenolysis

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Actions of cortisol in stress situations

Mobilizes fat, carbs and proteins

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Actions of epinephrine in stress

Mobilizes glucose via glycogenolysis and fat via lipolysis.

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Metabolic actions of cortisol

1) Protein catabolism and delivery of amino acids; 2) lipolysis and delivery ofr fatty acids and glycerol 3) gluconeogenesis raises glycemia; also inhibits glucose uptake.

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Permissive actions of cortisol

Enhances glucagon (without cortisol --> fasting hypoglycemia); enhances epinephrine (without cortisol -->hypotension)

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α-MSH

Stimulates melanocytes and causes darkening of skin. Synthesized along with ACTH from pro-opiomelanocortin.

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↑cortisol, ↓CRH, ↓ACTH, no hyperpigmentation

Primary hypercortisolism

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↓cortisol, ↑CRH, ↑ACTH, hyperpigmentation

Addison disease - primary hypocortisolism

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↑cortisol, ↓CRH, ↑ACTH, hyperpigmentation

Secondary hypercortisolism

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↓cortisol, ↑CRH, ↓ACTH, no hyperpigmentation

Secondary hypocortisolism

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↓cortisol, ↓CRH, ↓ACTH, no hyperpigmentation, symptoms of excess cortisol

Steroid administration

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Cushing syndrome

Protein depletion, weak inflammatory response, poor wound healing, hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, osteoporosis, purple striae, hirsutism, hypertension, hypokalemic alkalosis, buffalo hump

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Actions of aldosterone

↑Na channels in lumen of principal cells, ↑activity of Na/K ATPase of principal cells --> increases Na reabsorption. Also ↑ secretion of K and H leading to hypokalemic metabolic alkalosis.

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Addison disease

↑ ACTH, hyperpigmentation, hypotension (no aldosterone, no cortisol), hyperkalemic metabolic acidosis (no aldosterone), loss of body hair (no androgens), hypoglycemia, ↑ ADH secretion

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Causes of secondary hyperaldosteronism

CHF, vena cava constriction, cirrhosis, renal artery stenosis

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Primary hyperaldosteronism

Na and water retention, hypertension, hypokalemic metabolic alkalosis, ↓ renin and angiotensin, no edema due to pressure diuresis and natriuresis.

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Primary hypoaldosteronism

Na and water loss, hypotension, hyperkalemic metabolic acidosis, ↑ renin and angiotensin II, no edema

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Secondary hyperaldosteronism

↑ renin and angiotensin II, ↑ Na and water retention in venous circulation, edema

261

Factors that influence ADH secretion

↑ osmolarity --> ↑ ADH secretion; ↓ blood volume --> baroreceptors --> medulla --> ↑ ADH secretion

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Actions of ADH

Inserts water channels in luminal membrane of collecting ducts, increases reabsorption of water.

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Central diabetes insipidus

Not enough ADH secreted. Dilute urine is formed in spite of water deprivation. Responds to injected ADH.

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Nephrogenic diabetes insipidus

ADH is secreted but ducts are unresponsive to it. Dilute urine is formed in spite of water deprivation or injected ADH.

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SIADH

Excessive secretion of ADH in spite of low osmolarity. Concentrated urine is formed.

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↓ permeability of collecting ducts, ↑ urine, ↓ urine osmolarity, ↓ ECF, ↑ osmolarity

Diabetes insipidus

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↑ permeability of collecting ducts, ↓ urine, ↑ urine osmolarity, ↓ ECF, ↑ osmolarity

Dehydration

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↑ permeability of collecting ducts, ↓ urine, ↑ urine osmolarity, ↑ ECF, ↓ osmolarity

SIADH

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↓ permeability of collecting ducts, ↑ urine, ↓ urine osmolarity, ↑ ECF, ↓ osmolarity

Primary polydipsia

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Actions of ANP

Atrial stretch or ↑ osmolarity --> ANP secretion --> dilation of afferent, constriction of efferent --> ↑ GFR --> natriuresis; also decreases permeability of collecting ducts to water.

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Delta cells of the pancreas

Between alpha and beta cells, represent 5% of islets. Secrete somatostatin.

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Alpha cells of the pancreas

Near the periphery of the islets, represent 20%. Secrete glucagon.

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Beta cells of the pancreas

In the center of the islets, represent 60-75%. Secrete insulin and C peptide.

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Insulin receptor

Has intrinsic tyrosine kinase activity. Insulin receptor substrate binds tyrosine kinase, activates SH2 domain proteins: PI-3 kinase (translocation of GLUT-4), p21RAS.

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Tissues that require insulin for glucose uptake

Resting skeletal muscle and adipose tissue

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Tissues independent of insulin for glucose uptake

Brain, kidneys, intestinal mucosa, red blood cells, beta cells of the pancreas.

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Anabolic hormones

Insulin, GH/IGF-1, androgens, T3/T4, IGF-1 (somatomedin C)

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Effects of insulin on potassium

Increases Na/K ATPase uptake of K. Insulin + glucose used to treat hyperkalemia.

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Mechanism of insulin release

Glucose enters β cells and is metabolized --> ↑ ATP --> closes K channels --> ↑ depolarization --> ↑ Ca influx --> exocytosis of insulin.

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Factors that stimulate secretion of insulin

Glucose, arginine, GIP, glucagon

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Factors that inhibit insulin release

Somatostatin, norepinephrine via α1 receptors

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↑ glucose, ↑ insulin, ↑ C peptide

Type 2 diabetes

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↑ glucose, ↓ insulin, ↓ C peptide

Type 1 diabetes

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↓ glucose, ↑ insulin, ↑ C peptide

Insulinoma

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↓ glucose, ↑ insulin, ↓ C peptide

Factitious hypoglycemia (insulin injection)

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Actions of somatomedin C

Increases cartilage synthesis at epiphyseal plates (↑ bone length). Also ↑ lean body mass. Protein-bound and long half-life correlates to GH secretion. Also called IGF-1.

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Secretion of GH

Pulsatile during non-REM sleep; more frequent in puberty due to increased androgens; requires thyroid hormones; decreases in the elderly.

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Factors that stimulate GH secretion

Deep sleep, hypoglycemia, exercise, arginine, GHRH, low somatostatin

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Factors that inhibit GH secretion

Negative feedback by GH on GHRH; positive feedback on somatostatin by IGF-1

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Dwarfism

Due to GH insensitivity during prepuberty

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Acromegaly

Due to excess GH in postpuberty. Enlargement of hands, feet and lower jaw, increased proteins, decreased fat, visceromegaly, cardiac insuficiency.

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Composition of bone

Phosphate and calcium precipitate forming hydroxyapatite in osteoid matrix.

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Actions of PTH

Rapid actions: increases Ca reabsorption in distal tubules and decreases phosphate reabsorption in proximal tubules, thus lowering blood phosphate and lowering solubility product which leads to bone resorption and raises plasma Ca. Slow actions: increases number and activity of osteoclasts (via osteoclast activating factor released by osteoblasts), increases activity of alpha-1 hydroxylase in the proximal tubules which increases active vitamin D and absorption of Ca and phosphate in the instetines.

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Clinical features of primary hyperparathyroidism

↑ plasma Ca and ↓ plasma phosphate, phosphaturia, polyuria, calciuria (filtered load of Ca exceeds Tm), ↑ serum alkaline phosphatase, ↑ urinary hydroxyproline, muscle weakness, easy fatigability.

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Clinical features of primary hypoparathyroidism

↓ plasma Ca and ↑ plasma phosphate, hypocalcemic tetany due to increased excitability of motor neurons.

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↑ PTH, ↑ Ca, ↓ phosphate

Primary hyperparathyroidism. Causes: parathyroid adenoma (MEN I and II), ectopic PTH tumor (lung squamous CA)

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↓ PTH, ↓ Ca, ↑ phosphate

Primary hypoparathyroidism. Cause: surgical removal of parathyroid.

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↑ PTH, ↓ Ca, ↑ phosphate

Secondary hypoparathyroidism due to renal failure (no active vitamin D, decreased GFR)

299

↑ PTH, ↓ Ca, ↓ phosphate

Secondary hyperparathyroidism. Causes: deficiency of vitamin D due to bad diet or fat malabsorption.

300

↓ PTH, ↑ Ca, ↑ phosphate

Secondary hypoparathyroidism due to excess vitamin D.

301

Vitamin D synthesis

Dietary and skin cholecalciferol is hydroxylated by 25-hydroxylase in the liver and activated to 1,25 di-OH cholecalciferol by 1-alpha hydroxylase in the proximal tubules.

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Actions of 1,25 di-OH cholecalciferol

Increases Ca binding proteins by intestinal cells which increases intestinal reabsorption of Ca and phosphate. Also increases reabsorption of Ca in the distal tubules. Increased serum Ca promotes bone deposition.

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Osteomalacia

Underminerilized bone in adults due to vitamin D deficiency leads to bone deformation and fractures. Low calcium leads to secondary hyperparathyroidism.

304

Rickets

Underminerilized bone in children due to vitamin D deficiency leads to bone deformation and fractures. Low calcium leads to secondary hyperparathyroidism.

305

Excess vitamin D

Leads to bone reosprtion and demineralization

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Synthesis of thyroid hormones

1) Iodine is actively transported into follicle cell; 2) thyroglobulin is synthesized in the RER, glycosylated in the SER and packaged in the GA; 3) Peroxidase is found in the luminal membrane and catalizes oxidation of I-, iodination of thyroglobulin and coupling to form MITs and DITs; 4) iodinated thyroglobulin is stored in the follicle lumen.

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Structure of thyroid hormones

T4 has iodine attached to carbons 3 and 5 of both fenol rings; T3 has iodide attached to carbons 3 and 5 of the amino terminal fenol ring and the 3 prime carbon of the hydroxyl end fenol ring; reverse T3 has iodide in carbon 3 of the amino terminal fenol ring but not carbon 5.

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Secretion of thyroid hormones

Iodinated thyroglobulin is endocytosed from the lumen of the follicles into lysosomes. Thyroglobulin is degraded into amino acids, T3, T4, DITs and MITs. T4 and T3 are secreted in a 20:1 ratio. DITs and MITs are deiodinated and iodine is recycled.

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Transport of thyroid hormones

99% is bound to TBG, 1% is free. T4 has greater affinity for TBG and a half-life of 6 days. T3 has greater affinity for nuclear receptor and is the active form with a 1 day half-life. 50:1 T4/T3 ratio in periphery.

310

Activation and degradation of thyroid hormones

5' monodeiodinase activates T4 into T3. 5-monodeiodinase inactivates T4 into reverse T3.

311

Actions of thyroid hormones

↑ metabolic rate by ↑ Na/K ATPase except in brain, uterus and testes; essential for brain maturation and menstrual cycle; permissive for bone growth; permissive for GH synthesis and secretion; ↑ clearance of cholesterol; required for activation of carotene; ↑ intestinal glucose absorption; ↑ affinity and number of β1 receptros in the heart.

312

Effects of hypothyroidism in newborns

↓ dendritic branching and myelination lead to mental retardation.

313

Effects of hypothyroidism in juveniles

Cretinism results in ↓ bone growth and ossification --> dwarfism. Due to lack of permissive action on GH.

314

Control of thyroid hormone secretion

Circulating T4 is responsible for negative feedback of TSH by decreasing sensitivity to TRH. T4 is converted to T3 in the thyrotroph to induce negative feedback.

315

Effects of TSH

Rapid actions: ↑ iodide trapping, ↑ synthesis of thyroglobulin, ↑ reuptake of iodinated thyroglobulin, ↑ secretion of T4; late effects: ↑ blood flow to thyroid gland, ↑ hypertrophy of follicles and goiter.

316

↓ T4, ↑ TSH, ↑ TRH

Primary hypothyroidism; ↑ TSH is the more sensible index

317

↓ T4, ↓ TSH, ↑ TRH

Pituitary (secondary) hypothyroidism

318

↓ T4, ↓ TSH, ↓ TRH

Hypothalamic (tertiary) hypothyroidism

319

↑ T4, ↑ TSH, ↓ TRH

Pituitary (secondary) hyperthyroidism

320

↑ T4, ↓ TSH, ↓ TRH

Graves disease

321

Pathophysiology of iodine deficiency

Thyroid makes less T4 and more T3 so actions of T3 may be normal but low levels of T4 stimulate TSH secretion with development of goiter. Thus euthyroid with goiter.

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Clinical features of hypothyroidism

↓ basal metabolic rate with cold intolerance, ↓ cognition, hyperlipidemia, nonpitting myxedema (mucopolysacchride accumulation around eyes retains water), physiologic jaundice (↑ carotene), hoarse voice, constipation, anemia, lethargy

323

Clinical features of hyperthyroidism

↑ metabolic rate with heat intolerance and sweating, ↑ apetite with weight loss, muscle weakness, tremor, irritability, tachycardia, exophthalmos.

324

Leydig cells

Stimulated by LH; produce testosterone for peripheral tissues and Sertoli cells. Testosterone provides negative feedback for LH secretion by pituitary.

325

Sertoli cells

Stimulated by FSH; produce inhibins (inhibits secretion of FSH), estradiol (testosterone is converted by aromatase), androgen binding proteins and growth factors for sperm. Responsible for development of sperm in males. Also MIH in male fetus.

326

↓ sex steroids, ↑ LH, ↑ FSH

Primary hypogonadism or postmenopause.

327

↓ sex steroids, ↓ LH, ↓ FSH

Pituitary hypogonadism or constant GnRH infusion (downregulates GnRH receptors of pituitary.

328

↑ sex steroids, ↓ LH, ↓ FSH

Anabolic steroid therapy. LH supression causes Leydig cell atrophy with decreased Leydig testosterone which suppresses spermatogenesis.

329

↑ sex steroids, ↑ LH, ↑ FSH

Pulsatile infusion of GnRH

330

Fetal development of male structures

LH --> Leydig cells --> testosterone --> Wolffian ducts (internal male structures: epididymis, vasa deferentia ans seminal vesicles). Testosterone + 5-alpha reductase --> dihydrotestosterone --> urogenital sinus and external organs. MIH by Sertoli cells --> regression of Mullerian ducts and female structures.