Sp_Exam_2_Key_Slides

Steroid Hormones and Receptors

• Steroid hormones easily diffuse through lipid bilayers of cell membranes.

• Thyroid hormones are transported by cell membrane carriers.

• Receptors found in cytoplasm or nucleus change gene expression.

• Action of lipid-soluble hormones is slower than that of water-soluble hormones.

• No amplification cascade present.

• Gene expression: changed by binding of the hormone-receptor complex to specific DNA binding sites

Receptor Regulation

Downregulation

• Decreases total receptor sites, reducing responsiveness to prolonged agonist activation.

Upregulation

• Gradual increase in the number of receptor sites.

The Hypophyseal Portal System

• Connects hypothalamus to pituitary gland via capillary beds and veins.

• Key structures include the median eminence, portal veins, and hypophyseal arteries.

Hormone Regulation via Negative Feedback

• Hormone levels are maintained through negative feedback loops.

• Process:

  • Hypothalamus releases hormones.

  • Anterior pituitary gland produces pituitary hormones.

  • Target gland releases hormones influencing effector responses.

Thyroid Gland Structure

• Comprised of right and left lobes, isthmus, and located adjacent to the trachea.

Thyroid Stimulating Hormone (TSH) Regulation

• Thyrotropes release TSH due to hypothalamic thyrotropin-releasing hormone (TRH).

• TSH binds to receptors in thyroid follicle cells.

• Regulates thyroid function through negative feedback of TRH and TSH via T3 concentration.

Effects of Thyroid Hormones

• Metabolic Rate: Increased basal metabolic rate (BMR).

• Calorogenic: Increased heat production.

• Sympathomimetic: Activates the fight-or-flight response.

• Cardiovascular: Enhances heart responsiveness.

• Growth: Essential for normal development and growth.

• Nervous System: Critical for development and adult activity.

Goiters

• Abnormal enlargement of the thyroid gland due to various causes, primarily iodine deficiency.

Growth Hormone (GH) Regulation

• Hypothalamus prompts secretion of GH affecting liver and various body organs.

• This includes increased IGF-1 production, protein synthesis, and changes in carbohydrate metabolism.

Cortisol Regulation and Effects

• ACTH stimulates cortisol secretion from the adrenal cortex.

• Glucocorticoids: primarily cortisol, are involved in stress response, stimulating various metabolic processes while suppressing immune functions.

  • ↑Plasma proteins

  • ↑Catabolism

  • ↑Muscle breakdown

  • ↑Free fatty acids

  • ↑Blood glucose (from noncarbohydrates)

  • ↑SNS response

  • Suppresses - The immune & inflammatory systems

• Mineralocorticoids

  • Aldosterone: regulated by presence of angiotensin II

• Androgens: sex hormones

Antidiuretic Hormone (ADH)

• Osmoreceptors in the hypothalamus regulate ADH release.

• ADH increases water reabsorption in the kidneys, reducing blood osmolarity.

• Stimulates thirst response.

Diabetes Insipidus

• Results from insufficient ADH, leading to large volumes of dilute urine and potential severe fluid imbalances.

• Nephrogenic diabetes insipidus caused by unresponsive collecting tubules.

Parathyroid Hormone (PTH)

• Secretion stimulated by decreased blood calcium levels.

• PTH promotes calcium release from bones and increased reabsorption in kidneys.

• High blood calcium levels inhibit PTH secretion.

Melatonin Regulation

• Regulates circadian rhythms; secretion increases in darkness, decreases with light.

Blood Glucose Control

• Pancreatic islets manage insulin and glucagon secretion to regulate blood glucose levels post-meal and between meals.

• Insulin lowers blood glucose through cellular uptake, while glucagon raises it by converting glycogen to glucose.

Diabetes Mellitus

• Characterized by increased urine osmolarity, frequent urination (polyuria), and elevated blood glucose levels.

Blood Composition Overview

Key Proteins

• Albumin, Globulin, Fibrinogen.

Electrolytes

• Sodium, Chloride.

Normal pH

• 7.4 (normal range: 7.35 - 7.45).

Hematocrit Ranges

• Men: 40.7% - 50.3%, Women: 36.1% - 44.3%.

Erythrocytes (RBCs)

• Function: Buffer blood pH; main component is hemoglobin.

• Structural features: Small, biconcave disks enhance surface area.

• Development occurs exclusively in the bone marrow post-birth.

• Abt 97-98% of O2 is transported by RBCs

• Adult Hemoglobin

  • Two alpha chains

  • Two beta chains

  • each protein holds one iron containing heme group, oxygen binds to heme groups

• Hemoglobin

  • Two pairs of polypeptide chains, the globins, each with an attached heme molecule composed of iron and protoporphyrin

Red Blood Cell Characteristics

• RBCs are mainly composed of hemoglobin (95%) and lack a nucleus or mitochondria.

• Typical lifespan around 120 days, eventually destroyed in the spleen.

  • Phagocytes from the spleen, liver, bone marrow, lymph nodes ingest and destroy RBCs

    • Heme → processed to bilirubin

Blood Types Overview

• Type O: Lacks A and B antigens, has both anti-A and anti-B antibodies.

• Type A and B possess corresponding antigens with opposite antibodies.

• Type AB has both antigens and no antibodies.

Sickle Cell Anemia

Characteristics

• Inherited recessive disorder affecting the beta chain of hemoglobin.

• Sickle shape when oxygen levels are low; leads to occlusion of small arteries, pain, and anemia.

Platelet Function

• Essential for blood coagulation; formed by megakaryocyte fragmentation.

• Lifespan of approximately 10 days; regulated by thrombopoietin and IL-11.

Hemostasis Stages

Primary Hemostasis

• Initial response to injury; vasoconstriction and platelet plug formation.

Secondary Hemostasis

• Formation of a fibrin clot through intrinsic and extrinsic pathways.

Final state

• clot retraction

Coagulation Cascade

• Intrinsic pathway initiated by contact with altered endothelium; extrinsic pathway triggered by vascular trauma.

• Leads to fibrin formation via thrombin conversion.

Blood Coagulation Factors

• Synthesized by the liver; many factors require vitamin K for their synthesis.

Fibrinolysis

• Involves plasminogen and t-PA, breaking down fibrin clots.

• D-dimer indicates clot degradation.

Idiopathic Thrombocytopenia Purpura

• Manifestations: bleeding or indication of bleeding (bruising, petechia, etc)

• Diagnosis: complete blood count (platelets below 20,000) and bleeding studies

Cardiovascular Function

Heart Anatomy

• Overview of heart structures and flow of blood through systemic and pulmonary circuits.

• Systolic Phase: Heart contracts, BP increase, Blood moves out along vessels

• Diastolic Phase: Heart relaxes, BP decrease, blood fills heart

• Valves enable one way flow, contraction of papillary muscles prevent retrograde flow

Blood Flow Through the Heart

• Sequence of blood flow:

  1. Blood enters right atrium from superior and inferior venae cavae.

  2. Flows through right AV valve into right ventricle.

  3. Contraction forces pulmonary valve open.

  4. Blood flows to lungs via pulmonary trunk for gas exchange.

  5. Oxygenated blood returns to left atrium via pulmonary veins.

  6. Flows through left AV valve into left ventricle.

  7. Contraction forces aortic valve open, distributing blood to the body.

  8. Returns to right atrium via venae cavae.

The Pulmonary and Systemic Circuits

• Left Heart: Sends oxygenated blood from lungs to the body via aorta.

• Right Heart: Sends deoxygenated blood to the lungs via pulmonary trunk.

• Arteries that you can palpate:

  • temporal, carotid (neck), brachial, radial, femoral, pedal, posterior tibial

Ventricular Comparison

• Right Ventricle: Thinner wall; pumps blood to nearby pulmonary circuit.

• Left Ventricle: Thicker wall; pumps blood through systemic circulation requiring more pressure.

Arterial Blood Pressure Basics

• Systolic Pressure: Pressure during heart contraction.

• Diastolic Pressure: Pressure during heart relaxation.

• Pulse Pressure: systolic - diastolic

• Mean Arterial Pressure (MAP): Average pressure in a patient's arteries.

  • MAP = 1/3 systolic + 2/3 diastolic

• Cardiac output: heart rate x stroke volume

• Blood Pressure: Cardiac output x total peripheral resistance

Steps of Cardiac Muscle Cell Action Potential

1. Rapid Depolarization: Triggered by the influx of sodium (Na+) ions through voltage-gated sodium channels, leading to a rapid increase in membrane potential.

2. Plateau Phase: Calcium (Ca2+) ions enter the cell through voltage-gated calcium channels, balancing the outward flow of potassium (K+) ions, which prolongs depolarization and prevents rapid repolarization.

3. Repolarization: Inactivation of calcium channels and activation of potassium channels lead to an efflux of K+ ions, resulting in a return to resting membrane potential..

Hypertension Complications

• Can lead to stroke, vision loss, atherosclerosis, kidney failure, heart attack, and bone loss.

Blood Pressure Regulation

• Blood Pressure = CO x Systemic Vascular Resistance.

• Sys and diastole affect overall heart performance.

The Frank-Starling Law

• Describes the relationship between end-diastolic volume and stroke volume.

ECG and Cardiac Cycle

Electrocardiography

• Definition: A diagnostic tool that records the electrical activity of the heart over time using electrodes placed on the skin.

• Purpose: Used to detect heart rhythm abnormalities, issues with the heart's electrical conduction, and effects of drugs or heart diseases.

• Components of ECG:

  • P Wave: Represents atrial depolarization.

  • QRS Complex: Represents ventricular depolarization.

  • T Wave: Represents ventricular repolarization.

  • QT Interval: Electrical systole of the ventricles (varies inversely with HR)

  • PR Interval: time from the onset of atrial activation to onset of ventricular activation

Phases of Cardiac Cycle

• Ventricular systole- first phase: Contracting ventricles push AV Valves Close but not enough pressure to open semilunar valves (Isovolumetric contraction)

• Ventricular systole - second phase: ventricular pressure rises, semilunar valves open and blood leaves (ventricular ejection)

• Ventricular systole- late: ventricles relax and BP drops allowing closure of semilunar valves, isovolumetric relaxtion occurs

Specialized Conduction System of Heart

The specialized conduction system of the heart refers to the network of cells and fibers responsible for controlling the heart's rhythmic contractions by coordinating the electrical impulses that trigger the heart to beat. This system ensures the heart beats in a regular and synchronized manner.

1. SA Node (Sinoatrial Node):

   • Often referred to as the "natural pacemaker" of the heart.

   • Located in the right atrium, near the opening of the superior vena cava.

2. Atrial Internodal Pathways:

   • These are specialized pathways of conductive fibers that carry the electrical signal from the SA node to the AV node.

   • They help ensure the electrical impulse spreads quickly and evenly across both atria so they contract together.

3. AV Node (Atrioventricular Node):

   • Located at the junction of the atria and the ventricles, near the interatrial septum.

   • The AV node acts as a "gatekeeper," briefly delaying the electrical signal before it moves to the ventricles. This delay allows the atria to fully contract and fill the ventricles with blood before the ventricles contract.

   • The AV node also has a backup pacemaker function if the SA node fails.

4. Bundle of His:

   • After the AV node, the electrical impulse moves to the Bundle of His, a bundle of specialized fibers located in the interventricular septum (the wall between the left and right ventricles).

   • The Bundle of His transmits the electrical signal from the AV node to the ventricular muscle.

5. Ventricular Bundle Branches:

   • The Bundle of His splits into two branches: the left bundle branch and the right bundle branch.

   • These branches conduct the electrical signal down to the left and right ventricles, respectively.

6. Purkinje Fibers:

   • The bundle branches further divide into Purkinje fibers, which are fine, specialized fibers that spread throughout the walls of the ventricles.

   • Purkinje fibers transmit the electrical signal very rapidly to the myocardial cells (heart muscle cells) of the ventricles, causing them to contract and pump blood out of the heart.

extravascular compressive forces

• When the heart muscle (myocardium) contracts, it squeezes the blood vessels running through the heart, including the coronary arteries. This temporarily reduces blood flow to the heart. However, when the heart relaxes, the vessels open up, allowing blood to flow freely and supply the heart with oxygen. This process ensures the heart gets the blood it needs to keep functioning.

• Implications

  • Coronary flow occurs primarily in Diastole

  • Endocardium does most work

  • Endocardium has highest instramyocardial pressure

  • endocardium is vulnerable to ischemia

Pulmonary Embolism: A blockage in a pulmonary artery in the lungs resulting from blood clots that migrate from the legs or other body parts.

Heart Sounds: The sounds produced by the heart during each heartbeat, mainly the 'lub' (S1) from closing of the mitral and tricuspid valves and the 'dub' (S2) from closing of the aortic and pulmonary valves.

Atherosclerosis: condition characterized by the buildup of plaques, which are made up of fat, cholesterol, and other substances, in the walls of arteries. This buildup can lead to narrowing and hardening of the arteries, affecting blood flow. It is a major contributor to cardiovascular diseases, including heart attacks and strokes.

Bradycardia

• Definition: A slower than normal heart rate, typically defined as fewer than 60 beats per minute.

• Causes: Can result from sleep, medications, or heart conditions.

• Symptoms: May include fatigue, dizziness, or fainting.

Tachycardia

• Definition: An abnormally fast heart rate, generally above 100 beats per minute.

• Causes: Can be caused by stress, anxiety, fever, or heart abnormalities.

• Symptoms: May include palpitations, shortness of breath, or chest pain.

Ventricular Fibrillation

• Definition: A life-threatening heart rhythm that results in a rapid, uncoordinated contraction of the ventricles, preventing effective blood circulation.

• Symptoms: Sudden cardiac arrest, loss of consciousness, or no pulse.

• Treatment: Requires immediate medical intervention with CPR and defibrillation.

Myocardial infraction

• Sudden death of a patch of myocardium b/c of blockage of coronary circulation

  • Atheroma (blood clot/fatty deposit) obstructs coronary arteries

  • cardiac muscles below blockage dies

  • heavy pressure or squeezing pain on left arm

  • can lead to fibrillation and cardiac arrest

    • results in 27% of all deaths in US