Physiology Final Exam Exhaustive Study Guide

Reproductive Physiology in Women

Regarding reproductive physiology in women, the estrogens play a critical role in the proliferative phase of the menstrual cycle. Specifically, estrogens stimulate the proliferation of the endometrium and the synthesis of progesterone receptors. Progesterone, on the other hand, levels increase to cause hypertrophy of the endometrium, stimulate glandular secretion, and inhibit uterine contractions. A decrease in progesterone levels is the specific trigger for the vasoconstriction of the spiral arteries, which initiates the process of menstruation.

Libido in women is influenced by two main sources of hormones: androgénios produced by the adrenal gland (glândula supra-renal) and esteróides produced in the ovary. It is important to note that the production of specific hormones is localized. Estrogens are primarily secreted by the teca cells (and follicle), while progesterone is secreted by the corpo amarelo (corpus luteum). Both are essential for the maintenance of pregnancy.

Post-Menopause and Physiological Changes

The reduction of ovarian hormonal secretion during post-menopause causes several systemic changes. The derme, epiderme, and subcutaneous cellular tissue become thinner. While many functions decline, the synthesis of melanina actually increases (contrary to common misconceptions regarding a decrease). Cardiovascular risks also rise, making hypertension and atherosclerosis more frequent.

Vasomotor symptoms, such as sudden increases in heat (hot flashes) and sweating, are directly related to cutaneous vasodilation. In terms of fertility, it begins to decline approximately $10$ years before the actual onset of menopause. However, menstrual irregularities typically only begin to appear $3$ to $5$ years prior to the final cessation of the cycle. It is also important to distinguish between melanina and melatonina, which have distinct biological roles.

Physiology of Male Sex Hormones

The regulation of male sex hormones involves the hypothalamus-pituitary-gonadal axis. The GnRH (hormona libertadora de gonadotropina) is produced in the hypothalamus but is released in pulsatile bursts (peaks) rather than in a continuous flow. This hormone stimulates the adeno-hipófise (anterior pituitary) to release two major gonadotropins: LH (hormona luteinizante) and FSH (folículo-estimulante).

The neuro-hipófise (posterior pituitary) is not involved in this part of the axis, as it only releases vasopressina (ADH) and ocitocina. LH acts specifically on the células de Leyding to stimulate the production of testosterone. Once produced, testosterone exerts negative feedback on the hypothalamus to decrease the secretion of GnRH.

Inhibina is another regulatory hormone produced by the células de sertoli. It specifically inhibits the secretion of FSH at the pituitary level but does not reach the hypothalamus to inhibit GnRH. FSH itself is essential for promoting espermatogénese (the formation of sperm).

Bone Growth and Development

Bone growth occurs through specific mechanisms. Size increases through appositional growth, which involves the deposition of layer upon layer of bone material. While growth in thickness can continue, growth in length ceases once the placa epifisária (epiphyseal plate) is converted into the linha epifisária (epiphyseal line).

During development, osteoblasts of the periósteo form ridges separated by grooves that eventually fuse to form tunnels. These tunnels are subsequently filled with concentric lamellae. Several hormones are critical for stimulating bone growth, including growth hormone (hormona de crescimento), thyroid hormone (hormona tiroideia), estrogens, and progesterone.

Bone Repair and Remodeling

The process of bone repair occurs in distinct stages. The first phase involves the formation of a hematoma from blood released by damaged vessels. Following this, calluses form: the calo interno (internal callus) forms between the bone ends, while the calo externo (external callus) forms an osteocartilaginous ring around the fracture site.

The initial bone formed to replace these calluses is osso reticular (immature bone). This is later replaced by osso compacto/lamelar (mature bone) through the process of remodeling. Remodeling is the constant adaptation of bone to its mechanical function, and during this replacement process, parts of both the internal and external calluses are removed.

Calcium Regulation and Vitamin D

Plasma calcium levels are tightly regulated by several mechanisms. Hipocalcemia (low calcium) is the primary stimulus for the secretion of PTH (hormona paratiroideia). PTH increases plasma calcium by accelerating bone destruction (resorption) and increasing the reabsorption of calcium from the renal filtrate. It also increases the production of active Vitamin D.

Hypercalcemia (high calcium) triggers the release of calcitonina from the C cells (células parafoliculares) of the thyroid gland. Calcitonina works to lower plasma calcium by promoting the construction of bone matrix and drawing excess calcium from circulation. Active Vitamin D is essential as it stimulates the absorption of calcium in the small intestine (intestino delgado).

Regulation of Extracellular Fluid and Water

The osmolality of blood is a primary regulator of ADH (antidiuretic hormone) secretion. An increase in blood osmolality is the main stimulus for the hypothalamus to secrete ADH, which then increases water reabsorption in the kidneys, thereby decreasing blood osmolality. Conversely, the auricular natriuretic hormone (peptídeo natriurético auricular) acts to decrease the secretion of both ADH and aldosterona.

Blood pressure also influences these mechanisms. A sharp drop in blood pressure acts as a stimulus for ADH production to help retain water and increase vessel volume. Increased blood pressure would conversely decrease ADH secretion to lower the total volume. In terms of total body water, increased extracellular osmolality significantly boosts the thirst reflex mediated by the hypothalamus. Baroreceptors also stimulate thirst when blood pressure decreases.

Angiotensina II plays a multifaceted role: it induces the production of aldosterone and ADH, stimulates the reflex of thirst, increases salt appetite, and induces systemic vasoconstriction. The thirst reflex can be naturally inhibited by the distension of the digestive tract (signaling fluid intake) or the presence of a moist oral mucosa.

Sodium Balance and Natremia

Sódio (Sodium) is the dominant extracellular ion. While small amounts are lost via sweat, the major route for sodium excretion is through the urine. Aldosterone is the primary regulator of sodium; it primarily targets receptors in the tubo contornado distal (distal convoluted tube), although it has minor effects on the collecting duct. In contrast, ADH mainly acts on the tubo coletor.

The natriuretic hormone will decrease the reabsorption of sodium in these tubes to promote excretion. Medical terminology for sodium-related conditions includes: Hipernatrémia for high sodium, Hipercaliémia for high potassium, and Hipercalcemia for high calcium.

Cardiac Function Determinants and Regulation

Cardiac function is determined by several factors including pre-carga, which relates to venous return. A decrease in pre-load or venous return leads to a decrease in contraction force and cardiac output (débito cardíaco). Conversely, an increase in venous return increases the stroke volume (volume de ejeção), cardiac output, heart rate, and blood pressure.

Stimulation of the heart is also mediated by noradrenalina and adrenalina (sympathetic stimulation), which increase the heart rate. In cases of low blood pH due to increased $CO_2$, the body responds with sympathetic stimulation. This triggers the release of adrenaline from the adrenal medulla, increasing heart rate, stroke volume, and cardiac output, alongside peripheral vasoconstriction. This response ensures that blood is pumped more vigorously to improve oxygenation.

Smooth and Heart Muscle Characteristics

Smooth muscle cells (músculo liso) contain actin and myosin myofilaments but lack the striations seen in other muscles. They possess junções de hiato (gap junctions) and numerous cavéolas in the plasma membrane. Instead of troponin, they use calmodulina, a calcium-regulated protein that phosphorylates myosin. These cells can generate action potentials via spontaneous depolarization. Their calcium supply comes primarily from the extracellular environment, as their sarcoplasmic reticulum is quite rudimentary.

In contrast, skeletal muscle relies extensively on the sarcoplasmic reticulum for calcium. Cardiac muscle (músculo cardíaco) uses a combination of both the sarcoplasmic reticulum and extracellular calcium.

The Cardiac Cycle and Electrical Properties

The cardiac cycle consists of several stages. Isovolumetric contraction occurs between the closure of the auriculo-ventricular valve and the opening of the semilunar valve. Isovolumetric relaxation is the period between semilunar valve closure and AV valve opening. Ventricular filling has both passive and active phases; the active ventricular filling occurs in the final third of ventricular diastole when the atria contract to top off the ventricles.

The heart's rhythm is primarily set by the nódulo sino-auricular (sinus node), which generates action potentials at the fastest rate. The despolarização in pacemaker cells is primarily the result of calcium channel opening, not sodium. A foco ectópico refers to any area of the heart generating a beat other than the sinus node (including the AV node).

Thyroid Gland Function and Hormones

Thyroid hormones $T3$ and $T4$ are produced through a complex process. Iodine ions enter follicular cells via active transport (not facilitated). These ions are then linked to tyrosine and tiroglobina. The tiroglobina is secreted into the lumen of the follicle where iodinated tyrosine amino acids combine to form $T3$ and $T4$.

The parafollicular cells (C cells) are solely responsible for calcitonin and do not participate in thyroid hormone production. Once in the blood, $T3$ and $T4$ bind to transport proteins, primarily thyroxine-binding globulin ($70-75\%$) or albumin. In peripheral tissues, the non-functional $T4$ is converted into functional, active $T3$.

Adrenal Medulla and Stress Response

The adrenal medulla releases adrenaline, a catabolic hormone and a primary mediator of the stress response. Its functions include elevating blood glucose levels by catabolizing glycogen. Adrenaline also redirects blood flow toward major muscle masses by inducing vasodilation in the skeletal and cardiac muscles while causing vasoconstriction in the skin (cutaneous) and viscera. Noradrenalina, meanwhile, tends to cause vasoconstriction throughout the body.

Microcirculation and Capillary Types

Capillaries vary in structure to suit their location. Continuous capillaries have no gaps between endothelial cells and are found in muscles and nervous tissue. Fenestrated capillaries have numerous pores (fenestrae) and are located in intestinal villi and renal glomeruli. Sinusoidal capillaries have the largest diameters and large fenestrae with a thin basement membrane, found in endocrine glands where large hormones must pass. Sinusoides are specifically large sinusoidal capillaries in the liver and bone marrow. Seios venosos, found in the spleen (the site of red blood cell destruction), are larger than sinusoids.

Hemodynamics and Blood Flow Control

Blood flow is directly proportional to blood pressure differences and inversely proportional to peripheral resistance. Resistance increases with the length of the vessels or the viscosity of the blood and decreases with the increase of vessel diameter ($Flow \propto \frac{\Delta P}{R}$). Although small arteries have high resistance, the arteríolas collectively provide the highest resistance and are the most important for controlling arterial pressure due to their abundance.

The greatest percentage of blood volume is actually stored in the veins. While blood velocity is lowest in the veins, the cross-sectional area is actually largest in the capillaries. The aorta sees the highest velocity and pressure. Veins are characterized by high vascular compliance (distensibilidade).

Gastrointestinal Hormones and Emptying

Several hormones regulate duodenal and gastric function. Gastrina is the only hormone that promotes gastric emptying. Secretin promote pancreatic bicarbonate secretion and is stimulated by high acidity (low pH) in the pylorus. Colecistocinina (CCK) stimulates gallbladder contraction but, along with secretin and GIP, actually delays gastric emptying.

Motilin increases gastric motility and pyloric sphincter tone to ensure complete digestion. Somatostatin, however, decreases smooth muscle contraction. The entry of chyme into the duodenum inhibits gastric movements via hormonal release (CCK, secretin) and nervous reflexes.

Muscle Fiber Physiology and Contraction

Muscle fibers contain specialized proteins. Tropomiosina covers active sites on actin, while troponina consists of three subunits with affinities for actin, tropomyosin, and $Ca^{2+}$. Actina F is the filamentous form (double helix), while actina G is the specific molecule. A ponte cruzada (cross-bridge) forms when the myosin head (which contains ATPase) binds to an actin site.

Myosin filaments are found in the Banda A and are linked to the Disco Z via titina. The Zona H is the central part of the Banda A containing only myosin. Contraction types include:

1. Isométrica: Change in tension, no change in muscle length.
2. Isotónica: Change in length, no change in tension.
3. Concêntrica: Muscle shortens while tension increases.
4. Excêntrica: Muscle lengthens while tension gradually decreases.

Tónus muscular (muscle tone) is the maintenance of uniform tension over long periods, often associated with smooth muscle and sphincters.

Metabolism and Fiber Types

Fiber types are adapted for different activities. Type I fibers (contrações lentas) are intensely oxidative, containing many mitochondria, a rich capillary network, and high mioglobina; they are fatigue-resistant and ideal for long-distance exercise like marathons. Type II fibers (contração rápida) have higher glycogen reserves and are better adapted for anaerobic respiration and short, intense bursts.

Anaerobic respiration breaks down glucose into ATP and lactic acid in the absence of oxygen. Aerobic respiration is more efficient, requiring oxygen to produce ATP, $CO_2$, and water from glucose, fatty acids, and amino acids. An "oxygen debt" (carência de oxigénio) is created when extra oxygen is needed after exercise to restore cellular energy levels.

Renal Filtration and Acid-Base Balance

Glomerular filtration pressure is reduced by the constriction of afferent arterioles (arteríolas aferentes), which occurs during sympathetic stimulation (e.g., exercise). Filtration pressure is increased by high blood pressure, arterial dilation, or a decrease in plasma proteins.

The body maintains acid-base balance through multiple systems. The respiratory system reacts quickly but is less efficient, while the kidneys are slower but more powerful. H+ secretion into the filtrate and bicarbonate reabsorption increase extracellular pH. However, H+ secretion is inhibited if the urine pH drops below $4.5$.

Aldosterone also influences pH by promoting sodium-potassium ATPases, which increase sodium reabsorption and H+ or potassium excretion. Buffer systems include bicarbonate (ácido carbónico/bicarbonato), phosphates, and proteins like albumina and hemoglobina.

Blood Coagulation Mechanisms

Coagulation involves a cascade of factors. The intrinsic pathway starts when Factor XII contacts collagen. The extrinsic pathway is initiated by tissue thromboplastin (tromboplastina). Both converge on the common pathway starting with the activation of Factor X. The combination of activated Factor X, Factor V, phospholipids, and calcium forms protrombinase.

Protrombinase converts protrombina into trombina. Finally, trombina converts fibrinogénio into fibrina. Fibrinolysis, the destruction of a clot, is mediated by plasmina, which specifically hydrolyzes the fibrina (not the fibrinogen).

Questions & Discussion

True or False: Insulin receptors act on the external surface as enzymes? False. The portion of the receptor that acts as an enzyme to phosphorylate proteins is located on the internal surface of the plasma membrane.

True or False: Oxytocin produces milk? False. Ocitocina is responsible for uterine contractions and the expulsion of milk; actual milk production is governed by prolactin.

True or False: Calcium in skeletal muscle is removed to the extracellular environment? False. In skeletal muscle fibers, calcium is exclusively pumped back into the sarcoplasmic reticulum by the ATPase $Ca^{2+}$ (SERCA).

How do monosaccharides enter and exit intestinal cells? Glucose and galactose enter via secondary active transport (sodium symport), while frutose enters via facilitated diffusion. All exit the cells into circulation via facilitated diffusion.

What is the distinction between Functional Residual Capacity and Vital Capacity? Functional Residual Capacity is the sum of expiratory reserve volume and the volume remaining after a normal, restful expiration. Vital Capacity is the total sum of expiratory reserve, inspiratory reserve, and tidal volumes (everything except the absolute residual volume).

What mediates vascular spasms? Spasms result from smooth muscle contraction. Endotelina is a potent vasoconstrictor released by endothelial cells, but tromboxanos are specifically released by activated platelets.

Does gas diffusion depend only on thickness and surface area? No. While thickness and surface area are important, the rate depends fundamentally on the partial pressure gradient of the gas across the membrane.**