The disease chapters discuss the pathomechanisms of the diseases with an emphasis on metabolic changes and affected signaling pathways. They include many of the most common (by diagnosis), deadliest (by deaths), and most expensive (by cost of treatment) diseases.
Introduction
Metabolism of Human Diseases discusses metabolism and signaling pathways in tissues and organs known to be relevant to common human diseases. The diseases are selected to cover a wide spectrum of human diseases in the industrialized world (as described in the tenth edition of the International Classification of Diseases, ICD-10).
Anatomy and Physiology of the Brain
Overview
Astrocytes and the entire BBB protect neurons from toxic metabolites by preventing their transport into the brain through exclusion or effl ux and by neutralizing harmful compounds through enzymatic uptake or inactivation [1. Neuronal dysfunction and related neurological diseases can occur when the brain's stable metabolic environment is disrupted.
Brain-Specifi c Metabolic/Molecular Pathways and Processes
To exert their effects on the postsynaptic target, neurotransmitters first cross the synaptic cleft and then bind to specific postsynaptic receptors. The action of neurotransmitters is terminated by removing them from the synaptic cleft (Fig. 2.
Inside-In: Metabolites of the Brain Affecting Itself
Inside-Out: Metabolites of the Brain Affecting Other Tissues
Chapter 9 “Overview” under the section “Reproductive System”), and somatotropin/growth hormone (which directly affects adipocytes and the liver, see also the section “Overview” under the section. Relaxing or inhibitory hormones secreted by the hypothalamus act on the anterior the pituitary gland to regulate the release of these hormones into the bloodstream (see also the “Overview” section under the “Reproductive System” section).
Outside-In: Metabolites of Other Tissues Affecting the Brain
One of many examples of how the action of neurotransmitters mediates neuronal circuits and thereby regulates behavior is the dopaminergic reward system, which is called the mesolimbic pathway. The dopaminergic mesolimbic pathway is involved in diverse motivational behaviors, including those related to appetitive and aversive motivational processes [6.
Final Remarks
Introduction to Depressive Disorders
Pathophysiology of Depressive Disorders and Metabolic Alterations
Major Depressive Disorder
This activates lipoprotein lipase in visceral fat depots, which accumulates triglycerides in the internal area (see chapter "Hyperlipidemia") [9. Additionally, oxidative stress alters intracellular signaling, most notably Akt (also called protein kinase B) in the liver leading to aberrant efflux of glucose and triglycerides.
Treatment of Depressive Disorders
This vicious cycle is called the inflammatory and nitrosidative pathway and leads to increased neurodegeneration [16] and β-cell toxicity. Leptin is secreted by adipocytes and acts on the hypothalamus to reduce appetite and appetite (see chapter "Diabetes mellitus.
Infl uence of Treatment on Metabolism
The general mechanism of TCAs and the reuptake inhibitors is to prevent presynaptic reuptake of monoamines (5-HT, NE, DA), increasing their activity in the synaptic cleft. In addition, as additive treatment options, cortisol synthesis inhibitors could dampen the hyperactive HPA axis; anti-inflammatory drugs can reduce the damage caused by the inflammatory pathway and the nitrosidative pathway [16]; and the antidiabetic drug metformin could exert neuroprotective, neurotrophic and anti-inflammatory effects [23.
Perspectives
MT, Soczynska JK, Kim B, Lourenco MT, Kahn LS, Goldstein BI (2009) Metabolic syndrome and major depressive disorder: co-occurrence and pathophysiological overlap. Catena-Dell'Osso M, Bellantuono C, Consoli G, Baroni S, Rotella F, Marazziti D (2011) Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development.
Introduction to Schizophrenia
Pathophysiology of Schizophrenia and Metabolic Alterations
Schizophrenia
At a cellular level, changes in fine-tuning rather than underlying tissue loss or necrosis are observed, likely resulting from the convergence of genetic and environmental factors, leading to abnormal neuronal connectivity and synaptic signaling and altering dopaminergic pathways and glutamatergic neurotransmission. in the brain. Recent drug development is focusing on the glutamate system as a new and potentially (more) effective way to treat schizophrenia [9.
Treatment of Schizophrenia
Because dopamine affects many neurological systems in the brain (see above), antipsychotic and antidopaminergic treatments have broad therapeutic and adverse effects. First-generation antipsychotics (FGAs) work by inhibiting the binding of dopamine (DA), released from the hypothalamus, to D2 receptors in the pituitary gland.
Introduction to Epilepsy
Pathophysiology of Epilepsy and Metabolic Alterations
Epilepsy
As a result of those changes in astroglial physiology, the extracellular concentrations of K+ and Glu are increased, while those of adenosine are decreased. in particular, overexpression of adenosine kinase, the key enzyme for the metabolic clearance of adenosine by astrocytes, has been identified as a key pathological feature of epilepsy as it results in adenosine deficiency [2. In general, under any conditions of stress or distress. , the levels of adenosine rise, and it is this rise in adenosine that limits further neuronal energy consumption [4] by binding to.
Treatment of Epilepsy
Infl uence of Treatment on Metabolism
It is this unique metabolic modulation that is building excitement, not only for a deeper understanding of the ketogenic diet, but for metabolic manipulations in general as a novel. anticonvulsant strategy with good efficacy and few side effects. Schematic diagram illustrating ketone body formation from fatty acids present in the ketogenic diet and their subsequent use in the brain as fuel for ATP production.
Introduction to Parkinson’s Disease
Pathophysiology of Parkinson’s Disease and Metabolic Alterations
Parkinson’s Disease
Changes in the striatal levels of excitatory (glutamate) and inhibitory (γ-aminobutyric acid or GABA) neurotransmitters were found in another rodent model of Parkinson's disease, suggesting imbalanced neurotransmission in the basal ganglia of the disease. Parkinson's etiopathogenesis suggests the existence of defects in energy metabolism.
Treatment of Parkinson’s Disease
In a rodent model of PD, ions such as iron, manganese, copper and zinc are increased in the brain regions associated with the dopaminergic pathway [ 6. Deep brain stimulation (DBS), based on the implantation of electrodes mainly in the subthalamic nucleus in PD patients is the most common surgical treatment.
Infl uence of Treatment
Therefore, additional drugs are given to counteract side effects or to improve efficacy. Its use is limited to short periods of time because of the side effects seen at both the central level (cognitive decline) and peripheral level (tachycardia, meaning increased heart rate and constipation).
Olanow CW, Obeso JA (2012) The significance of defining preclinical or prodromal Parkinson's disease. Schapira AH (2011) Monoamine oxidase B inhibitors for the treatment of Parkinson's disease: a review of symptomatic and potential disease-modifying effects.
Introduction to Alzheimer’s Disease
Alzheimer’s Disease
Pathophysiology of Alzheimer’s Disease and Metabolic Alterations
Typical amyloid plaques in the brain parenchyma consist of Aβ fibrillar deposits (6) and apolipoproteins. Accumulation of Aβ in the brain may be due to increased production or decreased clearance or both.
Implications for Treatment and Infl uence of Treatment
Steiner H, Capell A, Leimer U, Haass C (1999) Genes and mechanisms involved in beta-amyloid generation and Alzheimer's disease. Introduction to the recommendations of the National Institute on Aging-Alzheimer's Association task forces on diagnostic guidelines for Alzheimer's disease.
Introduction to Migraine and Cluster Headache
Migraine and Cluster Headache
CH attacks often occur at fixed times of the day and night with a typical circadian periodicity. Although CH attacks are clearly distinguishable from migraine attacks, the two conditions share involvement of the trigeminovascular system at the peripheral level and disruption of pain-modulating structures in the brain.
Pathophysiology of Head Pain and the Trigeminovascular System
Alcohol; nitroglycerin, a vasodilator used in chronic heart failure (see chapter "Heart failure"); and exercise are recognized precipitants of acute cluster attacks. Today, both migraine and CH are considered neurovascular headaches, meaning they are caused by a complex series of neural but also vascular events.
Treatment of Migraine and Cluster Headache
Activation of 5-HT 1D receptors in nerve endings decreases the release of pro-inflammatory peptides such as CGRP and substance P. In recent years, neuroimaging findings and the introduction of neurostimulation for the treatment of primary headache, such as as migraine and CH have made significant contributions to better understanding the pathophysiology of these headache syndromes.
Introduction to Multiple Sclerosis
Multiple Sclerosis
Pathophysiology of Multiple
Sclerosis and Metabolic Alterations
In animal models of MS, the concentration of several metabolites in the CSF was altered. Similarly, the concentration of β-hydroxybutyrate (a ketone body and substrate for gluconeogenesis) is increased in the CSF of CIS patients corresponding to the presence of inflammatory lesions [9.
Treatment of Multiple Sclerosis
It is clear that several metabolic pathways are disrupted in the CNS of MS patients (see above). Noga MJ, Dane A, Shi S et al (2012) Cerebrospinal fluid metabolomics reveals changes in central nervous system metabolism in a rat model of multiple sclerosis.
Introduction to Down Syndrome
Pathophysiology of Down Syndrome and Metabolic
Down Syndrome
It has been hypothesized that the development of thyroid dysfunction in DS is influenced by oxidative stress [19] or deregulation of genes on chromosome 21 that participate in the immune response [20. Down syndrome is caused by triplication, mosaicism or translocation. of chromosome 21 and characterized by altered expression of genes on chromosome 21, but also other genes.
Treatment of Down Syndrome and Its Infl uence on Metabolism
Coskun PE, Busciglio J (2012) Oxidative stress and mitochondrial dysfunction in Down syndrome: relevance to aging and dementia. Kanavin OJ, Aaseth J, Birketvedt GS (2000) Thyroid hypofunction in Down syndrome: is it related to oxidative stress.
Anatomy and Physiology of the Eye
People can adjust their focus at different viewing distances by contracting the ciliary muscles, which ultimately leads to changes in the shape of the lens. They are nourished by diffusion from the aqueous humor, a clear, jelly-like fluid located in the anterior and posterior chambers of the eye.
Metabolic and Molecular Pathways and Processes in the Eye
Therefore, the energy consumption of the retina is four times higher in the dark than during illumination [6. Finally, the RPE is of utmost importance for the regeneration of the photoreceptor outer segments.
Inside-Out: Signals from the Eye Affecting Other Organs and Tissues
Retinoid-binding proteins transfer retinol from the outer segments to the RPE, where the rest of retinal metabolism occurs. Strong illumination of the outer segments in a high-oxygen environment can lead to photochemical damage.
Outside-In: Signals and Metabolites Affecting the Function of the Eye
The projection from the SCN to the pineal gland controls the release of melatonin, the "hormone of the night" involved in the regulation of our sleep-wake cycle. Circadian rhythm also affects body temperature, blood pressure and heart rate (see the chapters "Migraine and cluster headaches" and "Rheumatoid arthritis".
Introduction to Age-Related Macular Degeneration
Pathophysiology of Age-Related Macular Degeneration and
Age-Related Macular Degeneration
The complement system belongs to the innate immune system (see chapter "Overview" under part . "Immune system") and can be activated via three different pathways, i.e. the classical, lectin and alternative. It has been suggested that aging causes an increased activation of the alternative complement system in the blood [9.
Treatment of Age-Related Macular Degeneration
Ferris FL 3rd, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, Sadda SR (2013) Clinical classification of age-related macular degeneration. Maller JB, Fagerness JA, Reynolds RC, Neale BM, Daly MJ, Seddon JM (2007) Variation in complement factor 3 is associated with risk of age-related macular degeneration.
Introduction to Glaucoma
Glaucoma
Pathophysiology of Glaucoma and Metabolic Alterations
Treatment of Glaucoma
The relationship between metabolism and glaucoma is murky as most of the links examine the relationship between metabolism and elevated IOP, a risk factor for glaucoma, rather than glaucoma itself. With a projected increase in glaucoma incidence, this avenue represents one of the best hopes for reducing disease burden in the future.
Anatomy and Physiology of Teeth and Bones
The organic matrix of dentin is secreted by the odontoblasts that line the pulp cavity and extend the cell process to the dentin-enamel junction (Fig. 1a) [2. After primary dentin is finally complete in the root, odontoblasts continue to secrete dentin matrix, but at reduced rates.
Calcium and Phosphate Metabolism and Physiological Reactions in Bone
However, the enamel is supported by underlying dentin, which is more resilient and compensates for the brittleness of enamel. Shortly after eruption of the developing tooth, the enamel is more permeable and susceptible to acid dissolution.
Bone and Tooth: Roles in Calcium- Phosphate Homeostasis
However, the superficial layer of enamel repeats demineralization and remineralization (Fig. 1a) [2], especially when challenged (see chapter "Dental caries. An imbalance of calcium and phosphate metabolism in teeth and bone can potentially result in life-threatening conditions including caries (see chapter .. Dental caries ") and osteoporosis (see chapter.
Introduction to Dental Caries
Pathophysiology of Dental Caries and Metabolic Alterations
Dental Caries
Schematic drawing of the pore structure and changes in crystal appearance, due to dissolution, at each stage with the earliest stage on the right: translucent zone (1% mineral loss) through the dark zone (5% mineral loss) to the body of the lesion (20–50% mineral loss). The subsequently formed body of the lesion with even larger pores (20-30% mineral loss) represents continued dissolution of even the reprecipitated material as more acid pushes out of the plaque [13.
Treatment and Implications for Patients
Weatherell JA, Deutsch D, Robinson C, Hallsworth AS (1977) Assimilation of fluoride by enamel throughout the life of the tooth. Robinson C, Connell S, Kirkham J, Brookes SJ, Shore RC, Smith AM (2004) The effect of fluoride on the developing tooth.
Introduction to Osteoporosis
Pathogenesis of Bone Loss
Osteoporosis
IGF-1 is produced in the liver in response to growth hormone (somatotropin) from the pituitary gland (see chapter "Overview" under part "Brain") and consumption of animal protein from the diet, as a diet rich in amino acids is a common inducer of growth. Many cytokines, such as interleukin 1, interleukin 6 and tumor necrosis factor-α, are involved in the pathogenesis of osteoporosis.
Osteoporosis Treatment
Accordingly, a positive relationship was found between spontaneous protein intake in both men and women and bone mass at various skeletal sites [4. More recently, circulating serotonin from the gut has been shown to be inversely associated with BMD.
While hyperparathyroidism is associated with increased bone resorption, daily administration of teriparatide results in upregulation of skeletal bone formation. Possible adverse immune effects (dermatological side effects and skin infection) Hypocalcemia Possibly associated with osteonecrosis of the jaw and atypical femur fractures PTH Teriparatide Activators of bone formation: Osteoblast number and activity.
In the bony parts of embryonic cartilage, chondrocytes further differentiate and become hypertrophic. Then, a continuous cycle of bone remodeling begins, driven by the resorption of bone-forming osteoclasts and osteoblasts (see chapter "Overview" under the section "Teeth and Bones").
Joint-Specifi c Pathways and Processes
Damage to these structures due to a trauma usually leads to an impairment of the function of the joint and may result in changes in its biomechanical properties and subsequent osteoarthritis (see the chapter "Osteoarthritis") [ 16. The fibroblast-like type B synoviocytes line the synovial cavity with lubricating factors and produces components of the extracellular matrix, including hyaluronan, collagens and fibronectin.
Inside-In and Outside-In Signaling
This cell layer lacks a basement membrane and thus facilitates the rapid exchange of nutrients between the blood and the synovium. The substratum is intensively vascularized, providing nutrients to the synovium and avascular cartilage.
Metabolites Affecting the Joints
Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA 2nd, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L (2002) Cbfa1-independent decrease in proliferation of osteoblasts, osteopenia and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt co-receptor. Glass DA 2nd, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
Introduction to Osteoarthritis
Pathophysiology of Osteoarthritis
Osteoarthritis
In addition, the loss of integrity of the osteochondral junction is associated with microcracks and the invasion of articular cartilage by vascular channels originating from the subchondral bone, supporting the molecular cross-talk between the subchondral bone and the cartilage. After an initial phase of cartilage edema, cartilage damage and loss occurs, which is associated with synovial inflammation, osteophyte formation, and subchondral bone remodeling.
Osteoarthritis Management
Fast-acting symptomatic treatments for OA mainly consist of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Corticosteroids are potent anti-inflammatory drugs that inhibit, among other factors, phospholipase A2, reducing the release of proinflammatory native phospholipids.
Disease-Modifying Osteoarthritis Drugs
Choquette D, Wigler I, Rosner IA, Beaulieu AD (2000) Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. Brunell RM, Hayes CW, Brandt KD, Abramson SB, Manning PT, Miller CG, Vignon E (2013) A 2-year randomized, double-blind, placebo-controlled, multicenter study of the selective oral iNOS inhibitor, cindunistat ( SD - 6010), in patients with symptomatic osteoarthritis of the knee.
Introduction to Rheumatoid Arthritis
Pathophysiology of Rheumatoid Arthritis and Metabolic Alterations
Rheumatoid Arthritis
Left side: Androgens (such as testosterone) and estrogens (such as estrone and estradiol) originate from common precursors (see the “Overview” section under the “Reproductive System” section). The hypothalamic-pituitary-gonadal (HPG) axis involves the hypothalamic production of gonadotropin-releasing hormone, the subsequent secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary gland, and the subsequent synthesis of sex hormones (estrogens and androgens) in the female or male reproductive organs. glands (see chapter "Overview" under part . "Reproductive system").
Tailoring Rheumatoid Arthritis Management: Nighttime Modifi ed-
Straub RH, Cutolo M (2007) Circadian rhythms in rheumatoid arthritis: implications for pathophysiology and therapeutic management. Crofford LJ, Kalogeras KT, Mastorakos G, Magiakou MA, Wells J, Kanik KS, Gold PW, Chrousos GP, Wilder RL (1997) Circadian relationships between interleukin (IL)-6 and hormones of the hypothalamic-pituitary-adrenal axis: IL failure. -6 causes persistent hypercortisolism in patients with early untreated rheumatoid arthritis.
Anatomy and Physiology of the Gastrointestinal Tract
Gastrointestinal Tract-Specifi c Metabolic/Molecular Pathways
The practical importance of reabsorption is illustrated by patients who have undergone extensive small bowel resection. In such cases, small bowel to colon anastomosis usually reverses dependence on intravenous fluids.
Inside-In: Metabolites of the Gastrointestinal Tract Affecting
Digestion and absorption continue in the jejunum, where much of the electrolyte-rich fluid secreted by the stomach, pancreas, and duodenum is reabsorbed. The main function of the specialized colonic epithelium is to reabsorb H 2 O from the 3-6 l/day of liquid that enters the cecum, so that approx. 200 ml is excreted as faecal waste.
Outside-In: Metabolites of Other Tissues and External Factors
Inside-Out: Metabolites of the Gastrointestinal Tract Affecting
Typical Pathology of the Gastrointestinal Tract
Acute diseases, such as gastroenteritis (see chap. "Gastroenteritis"), usually do not cause nutritional deficiencies. Colorectal cancer (CRC, see the chapter "Colorectal Cancer") is a major cause of morbidity and mortality.
Introduction to Peptic Ulcer Disease
Peptic Ulcer Disease
Pathophysiology of Peptic Ulcer Disease and Metabolic Alterations
Treatment of Peptic Ulcer Disease
H2RAs block the stimulatory effect on acid secretion of histamine, released from enterochromaffin (ECL) cells. Histamine H 2 receptor (H 2 R) antagonists (H2RA) competitively and reversibly block H 2R and inhibit signaling via adenylate cyclase (AC) to reduce cAMP levels and thus H+ secretion.
Infl uence of Treatment on Metabolism and Consequences
Graham DY, Lew GM, Klein PD, Evans DG, Evans DJ Jr, Saeed ZA, Malaty HM (1992) Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcers. Chan FK, Ching JY, Suen BY, Tse YK, Wu JC, Sung JJ (2013) Effects of Helicobacter pylori infection on long-term risk of peptic ulcer bleeding in low-dose aspirin users.
Introduction to Gastroenteritis
Gastroenteritis
These viral pathogens are typically invasive, infecting enterocytes and causing cell death or toxic effects that disrupt normal intestinal function. Subsequent inflammation and disruption of the intestinal mucosa leads to watery diarrhea, inadequate digestion of food, and malabsorption of nutrients [18.
Treatment of Gastroenteritis
Prompt rehydration is key to stopping the continued deterioration of the gut and restoring normal metabolism. Proper digestion of food and absorption of nutrients can also help restore overall gut conditions, including normal bacterial flora.
Introduction to Lactose Intolerance
Lactose Intolerance
There is an increased use of fructose as a sweetener in many foods and beverages, and sensitivity to fructose can lead to symptoms similar to those of lactose intolerance. It is interesting that the symptoms that afflicted Charles Darwin for 50 years correspond exactly to those of lactose intolerance [6.
Pathophysiology of Lactose Intolerance and Metabolic
Lactose intolerance is often confused in babies with an allergy to milk proteins, especially αS1 casein, because the symptoms are similar [1. In IBD, it is not clear whether lactose intolerance is a cause or consequence of the intestinal inflammation.
Treatment of Lactose Intolerance
Removing lactose from the diet or taking digestive enzymes has no adverse effect on the patient's metabolism. Campbell AK, Matthews SB (2005) Tony's lactose-free cookbook: the science of lactose intolerance and how to live without lactose.
Introduction to Colorectal Cancer
Pathophysiology of Colorectal Cancer
Colorectal Cancer
Interestingly, the colonic microbiota (see chapter “ Overview ” under the section “Gastrointestinal Tract”) appears to play a crucial role in mediating the influence of diet on CRC (see below).
Pathophysiologic Role of the Colonic Microbiota
However, the microbiota can also produce harmful toxins and metabolites such as hydrogen sulfide (H2S), reactive oxygen species (ROS), and secondary bile acids (BAs) that promote inflammation and neoplastic progression (see below). . Impaired microbial composition and function results in a state of dysbiosis, a key precursor to diseases such as diabetes (see chapter "Diabetes mellitus"), obesity (see chapter Metabolic Syndrome), inflammatory bowel disease and KDF.
Treatment and Infl uence on Metabolism
O'Keefe SJ, Ou J, Aufreiter S et al (2009) Products of the gut microbiota mediate the effects of diet on colon cancer risk. Levin B, Lieberman DA, Mcfarland B et al (2008) Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.
Anatomy and Physiology of the Pancreas
Pancreas-Specifi c Metabolic Pathways and Processes
Microscopic view of the pancreas (stained with hematoxylin and eosin) showing the distinct exocrine (acinar, centroacinar, and duct cells) and endocrine (islet cells) compartments. c. This increases cellular ATP and the ATP/ADP ratio, inducing closure of the ATP-sensitive K+ channels.
Inside-In: Metabolites of the Pancreas Affecting Itself
In addition, characteristics of the subunits that make up the KATP channel also affect how insulin is secreted. Ultimately, the fine-tuned interactions between glucose transport and glucokinase activity and the characteristics of the ATP-sensitive K + channels and voltage-gated Ca 2+ channels contribute to the threshold that triggers insulin release in response to high blood glucose.
Outside-In: Metabolites of Other Tissues Affecting the Pancreas
Inside-Out: Metabolites of the Pancreas Affecting Other Tissues
Unlike the liver, the glucose released from the breakdown of glycogen in muscle is used only in skeletal muscle. The exocrine compartment (acinar, duct, and centroacinar cells) releases digestive enzymes and bicarbonate fluid to aid the gut.
Introduction to Diabetes Mellitus
Diabetes Mellitus
Pathophysiology of Diabetes Mellitus and Metabolic Alterations
Type 2 Diabetes
Two major pathophysiological features contribute to the manifestation of type 2 diabetes mellitus: insulin resistance (1) and β-cell dysfunction (2). Both insulin resistance and β-cell dysfunction develop in the setting of background genetic and environmental factors.
Diabetes Treatment and Its Infl uence on Metabolism
Treatment of type 2 diabetes mellitus (T2DM) usually begins with lifestyle intervention and an oral antidiabetic drug, typically metformin (1st step). Siren R, Eriksson JG, Vanhanen H (2012) Waist circumference a good predictor of future risk for type 2 diabetes and cardiovascular disease.
In the postabsorptive state, fatty acid oxidation provides energy for the liver; ketogenesis and ketone body release from the liver can provide energy for other organs, such as the brain (see chapter "Overview" . under the part "Brain"). High levels of BAs in the PC can activate the farnesoid X receptor (FXR) to reduce the BA load (by reducing uptake and increasing excretion, left PC).
Introduction to Cirrhosis
Pathophysiology of Cirrhosis and Metabolic Alterations
Cirrhosis
As a result, the port pressure increases, while the systemic blood pressure decreases (see chapter “Overview” under the section “Blood vessels”). As a compensatory response, the adrenergic system and the renin-angiotensin-aldosterone system (RAAS) are activated (see chapter . “Overview” under the “Kidney” section).
Treatment of Cirrhosis and Related Complications
The most effective treatments are splanchnic vasoconstrictive medications, which are based on the fact that the kidneys do not receive adequate blood flow due to fluid separation, relative hypovolemia, and increased renal resistance. The most common side effects of cathartics are dehydration which can worsen HE and kidney damage and electrolyte imbalance, especially hypokalemia (as the intestinal fluid contains high amounts of K + due to the secretion of K + and Cl - in the stomach) .
Conclusions and Perspectives
Hepatorenal syndrome is defined as the occurrence of renal failure in patients with advanced liver disease in the absence of an identifiable cause [19. It can be partially explained by a change in blood flow and vascular tone in the kidneys, secondary to PH.
Anatomy and Physiology of Fat Tissue
Fat Tissue-Specifi c Metabolic/
Molecular Pathways and Processes
Immunofluorescence images of WAT and BAT cross sections highlighting adipocyte size (2nd image), mitochondrial content (3rd image) and lipid droplet proteins (4th image). Transmission (5th image) and scanning (6th image) electron microscopy of WAT and BAT. b ): Anabolic (fat synthesis or lipogenesis) and catabolic (fat breakdown or lipolysis) pathways in adipocytes.
Inside-In: Metabolites of Fat Tissue Affecting Itself
These properties make adipose tissue a focus of intense investigation for the treatment of obesity and metabolic diseases. Adipose tissue is exquisitely designed for the regulated storage and release of lipid substrates and possesses all the cellular machinery for both fat synthesis (lipogenesis) and fat breakdown (lipolysis, Fig. 1b.
Inside-Out: Metabolites of Fat Tissue Affecting Other Tissues
This loss of adipose tissue homeostasis and the resulting changes in adipokines and fatty acids disrupt numerous metabolic processes, such as insulin signaling, thereby causing insulin resistance, glucose intolerance and other features of the metabolic syndrome (see section “Metabolic Syndrome”) [12. The autocrine and Thus, paracrine functions of adipose tissue are essential for maintaining adipose tissue homeostasis, but can lead to disease when overloaded.
Outside-In: Metabolites of Other Tissues Affecting Fat Tissue
Adipose tissue is thus a highly adaptive tissue that responds to both global and local needs in the body. 2 Interactions between adipose tissue and other tissues (Figure courtesy of Erin E. Kershaw and Gianna Paniagua) Overview.
Introduction to Metabolic Syndrome
Metabolic Syndrome
Since dyslipidemia, hyperglycemia, and hypertension are common disorders, these risk factors sometimes accumulate even in a lean individual without accumulation of visceral fat.
Pathophysiology of the Metabolic Syndrome
Treatment of the many risk factors involved in metabolic syndrome other than increased low-density lipoprotein cholesterol (LDLc, left side) aims to reduce visceral fat or directly targets individual risk factors. Reduction of visceral fat ameliorates dysregulation of several adipokines and the entire cluster of risk factors.
Treatment of Metabolic Syndrome and Impact on Metabolism
Kishida K, Funahashi T, Matsuzawa Y, Shimomura I (2012) Visceral adiposity as a target for the management of the metabolic syndrome. Inoue K, Maeda N, Kashine S, Fujishima Y, Kozawa J, Hiuge-Shimizu A, Okita K, Imagawa A, Funahashi T, Shimomura I (2011) Short-term effects of liraglutide on visceral fat, appetite and food preference: a pilot study. of obese Japanese patients with type 2 diabetes.
Anatomy and Physiology of the Lung
As the diameter of the bronchi decreases, a gradual transition in the architecture of the epithelium can be observed. As the goblet cells, glands, and elastic fibers decrease in number concurrently with the length of the cilia toward the smaller airways. The muscle layer increases temporarily. c.
Lung-Specifi c Metabolic/Molecular Pathways and Processes
Alveoli are subject to dramatic surface tension resulting from the attraction between molecules of the fluid film covering the surface of the alveolar cell. However, the stability of the alveoli is ensured by a surface-active substance (surfactant), which reduces the surface tension and lubricates the alveolar epithelium.
Outside-In: Metabolites of Other Tissues Affecting the Lung
The gradient of the substance is expressed by the partial pressure of gases (pO 2 , pCO 2 ) in the alveolar lumen and in the blood. Detection of blood gas status occurs primarily by arterial chemosensors located in the carotid artery (called the glomus caroticum) and also by central chemoception in the brainstem.
Inside-Out: Metabolites of the Lung Affecting Other Tissues
Of the three main indicators that trigger respiration (i.e. decreased pO2, increased pCO2 and increased H+/decreased pH), increased pCO2 is the most important signal. However, this effectively lowers the pCO2 in the blood, causing decreased respiration, which again causes hypoxemia or even apnea (lack of breathing).
