By S. Sebastian. Creighton University. 2018.
CHAPTER 28 The Physiology of the Liver 523 The Liver Can Modify or Amplify Hormone Action As discussed before discount 300mg isoniazid mastercard, the liver converts vitamin D3 to 25-hy- droxy vitamin D3 order 300mg isoniazid, an essential step before conversion to the active hormone 1 buy 300mg isoniazid otc,25-hydroxy vitamin D3 in the kidneys. The liver is also a major site of conversion of the thyroid hormone thyroxine (T4) to the biologically more potent hormone triiodothyronine (T3). The regulation of the he- patic T4 to T3 conversion occurs at both the uptake step and the conversion step. Due to the liver’s relatively large reserve in converting T4 to T3, hypothyroidism is uncom- mon in patients with liver disease. In advanced chronic liver disease, however, signs of hypothyroidism may be evident. The liver modifies the function of growth hormone (GH) secreted by the pituitary gland. Some growth hor- mone actions are mediated by insulin-like growth factors made by the liver (see Chapter 32). The Liver Removes Circulating Hormones The liver helps to remove and degrade many circulating hormones. Insulin is degraded in many organs, but the liver and kidneys are by far most important. The presence of in- sulin receptors on the surface of hepatocytes suggests that the binding of insulin to these receptors results in degrada- tion of some insulin molecules. There is also degradation of insulin by proteases of hepatocytes that do not involve the insulin receptor. The possible pathways followed by iron in Glucagon and growth hormone are degraded mainly by FIGURE 28. Both the liver and muscle contain liver secretes only items or incomplete statements in this glycogen, yet, unlike liver, muscle is (A) Chylomicrons section is followed by answers or by not capable of contributing glucose to (B) VLDLs completions of statements. Select the the circulation because muscle (C) LDLs ONE lettered answer or completion that is (A) Does not have the enzyme (D) HDLs BEST in each case. The first step in alcohol metabolism by the glucose it generates toxic to the body, it is transported in the liver is the formation of (C) Does not have the enzyme which of the following non-toxic acetaldehyde from alcohol, a chemical glucose-1-phosphatase forms? The hepatocyte is compartmentalized (E) Methionine and urea (D) Alcohol dehydrogenase to carry out specific functions. In patients with a portacaval shunt (E) Glycogen phosphorylase which subcellular compartment does (connection between the portal vein 2. The small intestine secretes various the circulating glucagon in these (E) 300 to 350 mg/dL triglyceride-rich lipoproteins, but the patients (continued) 524 PART VII GASTROINTESTINAL PHYSIOLOGY (C) Liver normally is the major site for (B) Conjugation of drugs with glycine (B) HDL receptors and then the removal of glucagon or taurine internalizing them (D) Small intestine produces more (C) Introduction of one or more polar (C) The albumin present on LDLs and glucagon in these patients groups to the drug molecule then internalizing them (E) Blood flow to the small intestine is (D) Introduction of one or more (D) The transferrin present on LDL compromised hydrophobic groups to the drug and then internalizing them 8. Which protein is made by the liver and molecule (E) The ceruloplasmin on LDLs and carries iron in the blood? The level of circulating 1,25- (B) Haptoglobin dihydroxycholecalciferol is SUGGESTED READING (C) Transferrin significantly reduced in patients with Arias IM. The Liver: Biology and Pathobi- (D) Ceruloplasmin chronic liver disease because ology. New York: Lippincott- (E) Lactoferrin (A) The liver can no longer efficiently Raven, 1994. The level of drug metabolizing convert 25-hydroxycholecalciferol to Black ER. Diagnostic strategies and test al- enzymes in the liver determines how 1,25-dihydroxycholecalciferol gorithms in liver disease. Clin Chem fast a drug is removed from the (B) The liver can no longer efficiently 1997;43:1555–1560. Therefore, it would be convert vitamin D to cholecalciferol Chang EB, Sitrin MD, Black DD. Gas- expected to find drug metabolizing (C) The liver can no longer efficiently trointestinal, Hepatobiliary, and Nutri- enzymes convert vitamin D to 25- tional Physiology. Philadelphia: Lip- (A) Higher in smokers than in hydroxycholecalciferol pincott-Raven, 1996. The detoxification enzyme sys- (B) Similar in smokers and nonsmokers convert cholecalciferol to 1,25- tems.
Some 6 NEUROTRANSMITTERS generic 300 mg isoniazid, DRUGS AND BRAIN FUNCTION classification is appropriate and the simplest and most commonly used is that based on chemical structure with the substances grouped as follows: Chemical group Examples A Choline ester Acetylcholine (ACh) B Monoamines Catechol Dopamine (DA) best 300 mg isoniazid, noradrenaline (NA) (adrenaline) Indole 5-Hydroxytryptamine (5-HT isoniazid 300mg low cost, serotonin) Imidazole Histamine (HIST) C Amino acids Acidic Glutamate (GLT) Basic g-Aminobutyric acid (GABA), glycine D Peptides Enkephalins, endorphins, cholecystokinin, substance P (Many others have been implicated) E Purines Adenosine triphosphate (ATP), adenosine In addition to the above it is now clear that the following substances may have an important central action but whether they can be classified as true neurotransmitters is uncertain: F Steroids Pregnenalone, dehydroepiandrosterone G Nitric oxide (A gas but it is always in solution in the brain) H Eicosanoids Prostaglandins A glance at the structure of the classical neurotransmitters (Fig. Although we will see that peptides certainly have some properties different from other NTs, in that they rarely have a primary neurotransmitter function and usually just complement the actions of those NTs in groups A±C, to put them in a class of their own and group all the others together simply on the basis of molecular size is inappropriate and misleading since it elevates the peptides to a status that is neither proven nor warranted. NEURONS: STRUCTURE AND ENVIRONMENT The neurons from which NTs are released number more than 7 billion in the human brain. Thus by giving off a number of branches from its axon one neuron can influence a number of others. All neurons, except primary sensory neurons with cell bodies in the spinal dorsal root ganglia, have a number of other, generally shorter, projections running much shorter distances among neigh- bouring neurons like the branches of a tree. The relatively simple structure of acetylcholine, the monoamines and the amino acids contrasts with that of the peptides, the simplest of which are the enkephalins which consists of five amino acids; substance P has eleven absence from sensory, i. Neuron cell bodies vary in diameter from 5 mm to 100 mm and axons from 0. Axons are generally surrounded by an insulating myelin sheath which is important for the propagation of action potentials generated in the neurons and gives the axons and the pathways they form a white colour which contrasts with the grey appearance of those areas of the CNS dominated by the presence of neuron cell bodies and their dendrites. The axon terminals of one neuron synapse with other neurons either on the dendrites (axo-dendritic synapse) or soma (axo-somatic synapse). Synapses on another axon 8 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION (a) Figure 1. N nucleus of neurons, O nucleus of oligodendrocyte, C capillary, D dendrite, G Golgi apparatus, M myelinated fibre, r ribosome, l lipofuscin pigment, g granular endoplasmic reticulum. The main features of a neuron are shown together with different synaptic arrangements (A) axo-dendritic, (B) axo-somatic, (C) axo-axonic and (D) dendro-dendritic. Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. Microtubules (about 20 nm in diameter) and solid neurofilaments (10 nm) extend from the cell body into the axon and are found along its length, although not continuous. They give structure to the axon but are not involved in the transport of material and vesicles to the terminal, which despite its high level of activity does not have the facility for molecular synthesis possessed by the cell body. Such transport is considered to be fast (200±400 mm per day), compared with a slower transport (1 mm per day) of structural and metabolic proteins. Although axonal flow is mainly towards the terminal (ortho or anterograde) there is some movement (fast) of waste material and possibly information on synaptic activity back to the cell body (retrograde). In addition to neurons the CNS contains various neuroglia (often just called glia). These can outnumber neurons by up to 10:1 in some areas and include star-like astro- cytes with their long cellular processess which not only enable them to provide structural support for the nerve cells but also facilitate NT degradation and the removal of metabolites. Oligodendrites are glial cells which are involved in myelin formation and although they also have long processes, these are spirally bound rather than extending out as in the astocytes. Neurons and glia are bathed in an ion-containing protein-free extracellular fluid which occupies less of the tissue volume (20%) in the brain than in other organs because of the tight packing of neurons and glia. In fact the whole brain is really suspended in fluid within its bony casing. The brain and spinal cord are covered by a thin close-fitting membrane, the pia mater and a thicker loose outer membrane, the dura mater. In the space between them, the subarachnord space, is the cerebrospinal fluid (CSF). This also flows into a series of ventricular spaces within the brain as well as a central canal in the cord and arises mainly as a secretion (ultra filtrate) of blood from tufts of specialised capillaries (the choroid plexus), which invaginate the walls of the ventricles.
They have a cir- (a) culating life span of only about 120 days cheap isoniazid 300 mg with mastercard, after which they are de- stroyed by phagocytic cells in the liver and spleen isoniazid 300mg mastercard. Oxygen molecules attached to hemoglobin molecules within erythrocytes give blood its red color purchase isoniazid 300mg visa. A hemoglobin molecule consists of four protein chains called globins, each of which is bound to one heme, a red-pigmented molecule. Each heme contains an atom of iron that can combine with one molecule of oxygen. Thus, the hemo- globin molecule as a whole can transport up to four molecules of oxy- gen. Considering that each erythrocyte contains approximately 280 million hemoglobin molecules, a single erythrocyte can transport over a billion molecules of oxygen. It is within the lungs that the oxygen mol- ecules contained in inhaled air attach to the hemoglobin molecules and are transported via erythrocytes to the trillions of body cells. Anemia refers to any condition in which there is an abnormally low hemoglobin concentration and/or erythrocyte count. The most common type is iron-deficiency anemia, which is due to a defi- cient intake or absorption of iron, or to excessive iron loss. In pernicious ane- mia, the production of red blood cells is insufficient because of lack of a substance needed for the absorption of vitamin B12 by intestinal FIGURE 16. Aplastic anemia is anemia due to destruction of the red bone electron micrograph. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 542 Unit 6 Maintenance of the Body Neutrophils Eosinophils Basophils Lymphocytes Monocytes Platelets Erythrocytes (thrombocytes) FIGURE 16. Leukocytes The leukocytes of the agranular type include monocytes and lymphocytes. Monocytes are the largest cells found in the blood, Leukocytes are larger than erythrocytes and are different in other and their large nuclei may vary considerably in shape. Leukocytes contain nuclei and mitochondria and have large nuclei surrounded by a relatively thin layer of cytoplasm. Because of their ameboid ability, leuko- cytes can squeeze through pores in capillary walls and move to an Platelets extravascular site of infection, whereas erythrocytes usually re- Platelets are the smallest of the formed elements and are actually main confined within blood vessels. Those leukocytes that have granules in their tion as platelets lack nuclei but, like leukocytes, are capable of cytoplasm are called granular leukocytes. The platelet count per cubic millimeter of small that they cannot be seen easily with the light microscope blood is 250,000 to 450,000. Platelets survive for about 5 to 9 are called agranular (or nongranular) leukocytes. Neutrophils are the most abundant Blood cell counts are an important source of information in as- type of leukocyte, constituting 54%–62% of the leukocytes in sessing the health of a person. As previously mentioned, an abnormally low red blood cell count is termed anemia. An ele- vated leukocyte count, called leukocytosis, is often associated with localized infection. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 Chapter 16 Circulatory System 543 FIGURE 16. Formed elements begin as hemocytoblasts (stem cells) and differentiate into the various kinds of blood cells, depending on the needs of the body. Circulatory System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 544 Unit 6 Maintenance of the Body TABLE 16. Neutrophil Nucleus with 2 to 5 lobes; cytoplasmic 54% to 62% of white cells present Phagocytic granules stain slightly pink 2. Eosinophil Nucleus bilobed; cytoplasmic granules 1% to 3% of white cells present Helps to detoxify foreign substances; stain red in eosin stain secretes enzymes that break down clots 3. Basophil Nucleus lobed; cytoplasmic granules Less than 1% of white cells present Releases anticoagulant heparin stain blue in hematoxylin stain Agranulocytes Cytoplasmic granules not visible; survive 100 to 300 days (some much longer) 1. Monocyte 2 to 3 times larger than red blood cell; 3% to 9% of white cells present Phagocytic nuclear shape varies from round to lobed 2. Lymphocyte Only slightly larger than red blood 25% to 33% of white cells present Provides specific immune response cell; nucleus nearly fills cell (including antibodies) Platelet Cytoplasmic fragment; survives 5 to 9 250,000 to 450,000/mm3 Enables clotting; releases serotonin, which (thrombocyte) days causes vasoconstriction Hemopoiesis under normal body conditions.
Esti- ume of filtrate (about 20% of the entering plasma flow) is mates of average 300mg isoniazid amex, normal values for pressures in the human pushed out of the capillary and the proteins remain in the kidney are: PGC generic isoniazid 300mg otc, 55 mm Hg; PBS purchase isoniazid 300 mg without prescription, 15 mm Hg; and COP, 30 circulation. From these values, we calculate a net ultrafiltration poses the outward movement of fluid. In the skeletal muscle capillary, the colloid osmotic pres- sure hardly changes with distance, since little fluid moves across the capillary wall. In the “average” skeletal muscle The Pressure Profile Along a Glomerular capillary, outward filtration occurs at the arterial end and Capillary Is Unusual absorption occurs at the venous end. At some point along the skeletal muscle capillary, there is no net fluid move- Figure 23. Filtration pressure equilibrium probably is not at- illary in other vascular beds (in this case, skeletal muscle). Also, capillary hydrostatic pres- sure declines little (perhaps 1 to 2 mm Hg) along the length Several Factors Can Affect GFR of the glomerular capillary because the glomerulus contains many (30 to 50) capillary loops in parallel, making the re- The GFR depends on the magnitudes of the different terms sistance to blood flow in the glomerulus very low. Therefore, GFR varies with changes in K ,f skeletal muscle capillary, there is a much higher resistance hydrostatic pressures in the glomerular capillaries and Bow- A. The middle line is the sum of PBS and the capillary and a glomerular capillary. The differ- the typical skeletal muscle capillary, filtration occurs at the arte- ence between PGC and PBS COP is equal to the net ultrafiltra- rial end and absorption at the venous end of the capillary. In the normal human glomerulus, fil- stitial fluid hydrostatic and colloid osmotic pressures are neg- tration probably occurs along the entire capillary. Assuming that lected here because they are about equal and counterbalance each Kf is uniform along the length of the capillary, filtration rate other. B, In the glomerular capillary, glomerular hydrostatic pres- would be highest at the afferent arteriolar end and lowest at the sure (PGC) (top line) is high and declines only slightly with dis- efferent arteriolar end of the glomerulus. The bottom line represents the hydrostatic pressure in 390 PART VI RENAL PHYSIOLOGY AND BODY FLUIDS man’s capsule, and the glomerular capillary colloid osmotic plasma proteins (e. The glomeru- lar blood flow has important effects on GFR is that the lar ultrafiltration coefficient (Kf) is the glomerular equiva- COP profile is changed along the length of a glomerular lent of the capillary filtration coefficient encountered in capillary. It depends on both the hydraulic conductivity glomerular blood flow were low. Filtering a small volume (fluid permeability) and surface area of the glomerular filtra- out of the glomerular capillary would lead to a sharp rise tion barrier. In chronic renal disease, functioning glomeruli in COP early along the length of the glomerulus. As a are lost, leading to a reduction in surface area available for fil- consequence, filtration would soon cease and GFR would tration and a fall in GFR. On the other hand, a high blood flow would al- mones appear to change glomerular Kf and, thus, alter GFR, low a high rate of filtrate formation with a minimal rise in but the mechanisms are not completely understood. In general, renal blood flow and GFR change hand in hand, but the exact relation between GFR and renal Glomerular Capillary Hydrostatic Pressure. Glomerular blood flow depends on the magnitude of the other fac- capillary hydrostatic pressure (PGC) is the driving force for tors that affect GFR. Be- cause of autoregulation, P and GFR are maintained at rel- Several Factors Contribute to the High GFR GC atively constant values when arterial blood pressure is var- in the Human Kidney ied from 80 to 180 mm Hg. Below a pressure of 80 mm Hg, The rate of plasma ultrafiltration in the kidney glomeruli however, PGCand GFR decrease, and GFR ceases at a blood (180 L/day) far exceeds that in all other capillary beds, for pressure of about 40 to 50 mm Hg. One of the classic signs several reasons: of hemorrhagic or cardiogenic shock is an absence of urine 1) The filtration coefficient is unusually high in the output, which is due to an inadequate PGC and GFR. Compared with most other capillaries, the The caliber of afferent and efferent arterioles can be glomerular capillaries behave as though they had more altered by a variety of hormones and by sympathetic pores per unit surface area; consequently, they have an un- nerve stimulation, leading to changes in PGC, glomerular usually high hydraulic conductivity. Some hormones act preferentially 2 filtration barrier area is large, about 2 m. Afferent arteriolar dila- 2) Capillary hydrostatic pressure is higher in the tion increases glomerular blood flow and PGC and, there- glomeruli than in any other capillaries. Afferent arteriolar 3) The high rate of renal blood flow helps sustain a high constriction produces the exact opposite effects. Efferent GFR by limiting the rise in colloid osmotic pressure, favoring arteriolar dilation increases glomerular blood flow but filtration along the entire length of the glomerular capillaries.
Although only limited motion is possible at each intervertebral joint 300mg isoniazid free shipping, the combined Dental vessels movement of all of the joints of the vertebral column results in and nerve extensive spinal action generic 300mg isoniazid mastercard. Articulations © The McGraw−Hill Anatomy buy isoniazid 300 mg free shipping, Sixth Edition Companies, 2001 200 Unit 4 Support and Movement Synchondroses that do not ossify as a person ages are those Proximal epiphysis of humerus that connect the bones of the floor and sides of the cranium and include the joints between the occipital, sphenoid, temporal, and Proximal epiphyseal plate (site of synchondrotic joint) ethmoid bones. In addition, the costochondral articulations be- tween the ends of the ribs and the costal cartilages that attach to the sternum are examples of synchondroses. Elderly people often exhibit some ossification of the costal cartilages of the rib cage. This may restrict movement of the rib cage and obscure an image of the lungs in a thoracic radiograph. Discuss the function of the pad of fibrocartilage in a sym- Body of physis and give two examples of symphyses. SYNOVIAL JOINTS The freely movable synovial joints are enclosed by joint capsules containing synovial fluid. Based on the shape of the articular sur- faces and the kinds of motion they permit, synovial joints are cate- Distal epiphyseal gorized as gliding, hinge, pivot, condyloid, saddle, or plate ball-and-socket. Distal epiphysis Objective 8 Describe the structure of a synovial joint. The function of synovial joints is to pro- occurs at both the proximal and distal epiphyseal plates. The mitotic activity at synchondrotic joints is responsible for bone growth in vide a wide range of precise, smooth movements, at the same length. Synovial joints are the most complex and varied of the Synchondroses three major types of joints. A totally ossified synchondrosis may also be ness of the associated ligaments and tendons; and referred to as a synostosis. Range of motion at synovial joints is characterized involves the mitotically active epiphyseal plate of a synchondrotic by tremendous individual variation, most of which is related joint. If such an injury is left untreated, bone growth is usually to body conditioning (fig. Excessive obesity may also retarded or arrested, so that the appendage will be shorter than normal. Although some people can perform remarkable contortions and are said to be “double-jointed,” they have no extra joints that help synchondrosis: Gk. Articulations © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 Chapter 8 Articulations 201 Arthroplasty is the surgical repair or replacement of joints. Ad- vancements in this field continue as new devices are devel- oped to restore lost joint function and permit movement that is free of pain. A recent advancement in the repair of soft tissues involves the use of artificial ligaments. A material consisting of carbon fibers coated with a plastic called polylactic acid is sewn in and around torn ligaments and tendons. This reinforces the traumatized struc- tures and provides a scaffolding on which the body’s collagenous fibers can grow. As healing progresses, the polylactic acid is ab- sorbed and the carbon fibers break down. Structure of a Synovial Joint Synovial joints are enclosed by a joint capsule (articular capsule) composed of dense regular connective tissue. Each joint capsule encloses lubricating synovial fluid contained within the joint cavity (fig. The term synovial is derived from a Greek word meaning “egg white,” which this fluid resembles. Patellar tendon Patella Synovial membrane Subcutaneous Articular prepatellar cartilage bursa Infrapatellar Meniscus fat pad Joint Subcutaneous cavity infrapatellar filled with bursa synovial fluid Infrapatellar bursa Tibia Patellar ligament Creek FIGURE 8. Articulations © The McGraw−Hill Anatomy, Sixth Edition Companies, 2001 202 Unit 4 Support and Movement a thin synovial membrane that lines the inside of the joint cap- in the direction of the other toes. Synovial fluid is similar to interstitial fluid (fluid between nied by the formation of a bunion at the medial base of the proximal phalanx of the hallux. It is rich in hyaluronic acid and albumin, and also callus that develops in response to pressure and rubbing of a shoe. The bones that articulate in a synovial joint are capped with a smooth layer of hyaline cartilage Kinds of Synovial Joints called the articular cartilage. Articular cartilage is only about 2 Synovial joints are classified into six main categories on the basis mm thick.
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