Physiology: Blood and Body Fluids

Comprehensive practice flashcards covering the entirety of the 1st-year medical physiology lecture on blood, body fluids, homeostasis, plasma proteins, erythrocytes, hemoglobin, iron metabolism, hemostasis, coagulation, and blood groups.

What is the definition of Human Physiology?

The study of functions of organs & systems and their integration and control.

What percentage of total body weight is accounted for by Total Body Water (TBW) in an adult male?

$60\%$ of total body weight.

What percentage of total body weight is Total Body Water (TBW) in females, obese individuals, and infants?

In females and obese individuals, TBW is $50\%$ of body weight (due to a higher content of fat); in infants, TBW is $75\%$ of body weight.

What percentage of total body mass is composed of solids, and what is their percentage composition?

Solids constitute the remaining $40\%$ of body mass: $18\%$ proteins, $15\%$ fats, and $7\%$ minerals.

According to the body mass diagram, what are the proportions and percentages of Intracellular Fluid (ICF) and Extracellular Fluid (ECF)?

Intracellular fluid (ICF) represents $2/3$ ($40\%$ of body mass), while Extracellular fluid (ECF) represents $1/3$ ($20\%$ of body mass).

What are the two subdivisions of Extracellular Fluid (ECF) and their respective shares of total body weight?

Intravascular fluid (plasma / "IVF"), which represents $5\%$ of body weight ($20\%$ of ECF), and interstitial fluid ("ISF"), which represents $15\%$ of body weight ($80\%$ of ECF).

What are the main cations and main anions in the Intracellular Fluid (ICF) versus Extracellular Fluid (ECF)?

Main cations: ICF has $\text{K}^+$ & $\text{Mg}^{2+}$; ECF has $\text{Na}^+$ & $\text{Ca}^{2+}$. Main anions: ICF has Phosphate & proteins; ECF has $\text{Cl}^-$ & $\text{HCO}_3^-$.

What mathematical formula expresses Fick's principle for the determination of compartment volume (volume of distribution)?

$$\text{Vol. of compartment (vol. of distribution)} = \frac{\text{Amount injected}}{\text{conc. in plasma}}$$

What three properties must an injected indicator possess when measuring fluid volume using Fick's principle?

The indicator must be inert, not toxic, and not utilized.

Which indicators are used clinically to measure Total Body Water (TBW), Extracellular Fluid (ECF), and Plasma volume?

TBW is measured with heavy water or antipyrine; ECF is measured with inulin or $\text{Na thiocyanate}$; Plasma is measured with Evan's blue dye or plasma proteins labeled with radioactive iodine.

How are the volumes of Intracellular Fluid (ICF) and Interstitial Fluid (ISF) calculated indirectly?

$\text{ICF} = \text{TBW} - \text{ECF}$ and $\text{ISF} = \text{ECF} - \text{Plasma}$.

In the volume of distribution example shown in the figure, what is the calculated apparent volume if $1000\,\text{mg}$ is injected and reaches a plasma concentration of $50\,\text{mg/L}$?

$\text{Volume} = \frac{1000\,\text{mg}}{50\,\text{mg/L}} = 20\,\text{L}$.

What is the definition of homeostasis, and what happens if it fails?

Keeping conditions in the internal environment (ISF) constant. Failure to achieve homeostasis leads to disease and ultimately death.

How are body temperature and internal pH maintained constant in the body?

Temperature is maintained constant by the balance between heat loss and heat gain; pH is kept constant by chemical buffers.

What are the two fluid exchanges involved in maintaining homeostasis?

1. Through the cell membrane: between cells & ISF; 2. Through the capillary membrane: between ISF & blood.

What are the sequential components of a biological homeostatic control system?

$\text{Stimulus (change)} \rightarrow \text{Receptor (detect stimulus)} \rightarrow \text{Center} \rightarrow \text{Effector organ(s)}$.

In the homeostatic control mechanism shown in the diagram, what pathway carries input to the control center, and what pathway carries output to the effector?

Input is sent via the afferent pathway; output is sent via the efferent pathway.

How do negative and positive feedback mechanisms differ in action, prevalence, and importance?

Negative feedback changes the variable back to its original state or "ideal value" and accounts for almost all control systems. Positive feedback increases the response to accelerate processes that must be completed rapidly (e.g., blood clotting and childbirth).

What is the normal blood volume in adult males and females, and what percentage of body weight does it represent?

$5\,\text{L}$ in adult males and $4.5\,\text{L}$ in adult females, representing $8\%$ of body weight.

What are the four primary functions of blood?

1. Transport (main function: carries $\text{O}_2$, $\text{CO}_2$, glucose); 2. Defensive (WBCs defend against micro-organisms and tumors); 3. Homeo-static (constant heat by distribution, ions); 4. Hemo-static (substances in blood act to stop bleeding).

What is the normal pH of blood, and what are its two main components by percentage?

Blood pH is slightly alkaline at $7.4$. It is composed of Plasma ($55\%$ fluid) and Cells ($45\%$: RBCs, WBCs, and platelets).

What is the volume, percentage of body weight, and general composition of plasma?

Yellow clear fluid with a volume of $3.5\,\text{L}$ ($5\%$ of body weight), composed of Water ($90\%$), Organic substances ($9.1\%$: plasma proteins, lipids, glucose, amino acids, vitamins, enzymes, waste products), and Inorganic constituents ($0.9\%$).

What are the chief inorganic ions and dissolved gases found in blood plasma?

Chief cation is $\text{Na}^+$; chief anions are $\text{Cl}^-$ and $\text{HCO}_3^-$. Dissolved blood gases are $\text{O}_2$, $\text{CO}_2$, and $\text{N}_2$.

What is the normal concentration of plasma proteins, and what are their sites of formation?

Normal concentration is $7.2\text{--}7.4\,\text{gm/dL}$. Sites of formation: 1. Liver: synthesizes Albumin, fibrinogen, prothrombin, and $50\%$ of Globulins ($\alpha$ & $\beta$); 2. Plasma cells of lymphoid tissues: synthesize $50\%$ of Globulins (gamma / $\gamma$).

According to the plasma fraction diagram, what are the normal concentration ranges for albumins and fibrinogen?

Albumins: $35\text{--}50\,\text{g/l}$; Fibrinogen: $2\text{--}4\,\text{g/l}$.

What is the normal Albumin/Globulin (A/G) ratio, and in what clinical conditions does it decrease?

Normally $1.2\text{--}1.6$. It decreases in: 1. Liver diseases (cirrhosis & infective hepatitis: decreased albumin production); 2. Kidney diseases (nephrosis: small-sized albumin lost in urine); 3. Infections (increased immunoglobulins / gamma globulins).

What is the total osmotic pressure of plasma, and what are its colloidal and crystalloid components?

Total osmotic pressure is $290\,\text{mmol/L} = 5000\,\text{mmHg}$. Colloidal (oncotic) pressure is $25\text{--}28\,\text{mmHg}$ (exerted by plasma proteins); crystalloid pressure constitutes the remaining pressure (exerted by $\text{Na}^+$, $\text{Cl}^-$, $\text{HCO}_3^-$).

Why is colloidal (oncotic) pressure biologically more effective in regulating fluid exchange than crystalloid pressure?

Because plasma proteins have a large molecular weight and cannot diffuse through the capillary membrane, keeping them inside blood vessels to regulate fluid exchange across capillaries.

Why is albumin the most important plasma protein for generating oncotic pressure?

Because it has the greatest concentration and the smallest molecular weight (osmotic pressure depends on the concentration/number of particles, not their size).

How does the viscosity of blood and plasma compare to water, and what determines blood viscosity?

Blood is $3\text{ times}$ as viscous as water; plasma is $1.5\text{ times}$ as viscous as water (maintains normal ABP). Viscosity is determined by: 1. RBCs (decreased in anaemia, increased in polycythemia); 2. Plasma proteins (fibrinogen most, due to large molecular size and elongated shape).

What are the transport, defensive, and capillary functions of plasma proteins?

Transport: Albumin & globulins ($\alpha$ & $\beta$) carry hormones and minerals, preventing loss in urine and providing a reservoir. Defensive: $\gamma$-globulins (antibodies) provide humoral immunity against microorganisms. Capillary: partially block capillary membrane pores, decreasing permeability.

How do plasma proteins function as blood buffers?

They account for $15\%$ of blood buffering power. Their buffer system consists of proteinic acid (weak acid) and sodium proteinate (strong base). At normal blood pH ($7.4$), plasma proteins are negatively charged and act as weak acids (anions).

What physiological process is illustrated in the diagram showing amino acid and protein fluxes between tissue cells, blood, and liver cells?

Plasma proteins serve as a source of amino acids for tissues, allowing rapid replacement of tissue proteins when they are depleted.

Why are erythrocytes called corpuscles rather than true cells, and what do they contain?

They are called corpuscles because they lack nuclei, ribosomes, and mitochondria. They contain potassium ($\text{K}^+$), hemoglobin, and the carbonic anhydrase enzyme for $\text{CO}_2$ transport.

What are the normal RBC counts in males and females, and when do counts physiologically increase or decrease?

Normal count: $5\text{ million/mm}^3$ in males, $4.5\text{ million/mm}^3$ in females. Count increases in newborns, athletes, and at high altitudes; count decreases in old age and growing children.

What is normal hemoglobin content in males, females, and newborns, and what does the term define?

Hemoglobin content is the amount of Hb in $100\,\text{mL}$ of blood: $15\text{--}16\,\text{g/dL}$ in males, $13\text{--}14\,\text{g/dL}$ in females, and $19\,\text{g/dL}$ in newborns (due to relative intrauterine hypoxia).

What cellular morphology and internal substance are identified in the erythrocyte diagram?

Biconcave red blood corpuscles with cytoplasm containing haemoglobin.

What percentage of an erythrocyte's weight is hemoglobin, and what are the polypeptide chains and adult proportions of HbA1 and HbA2?

Hemoglobin is $34\%$ of RBC weight. Adult HbA1 has $2\text{ alpha and }2\text{ beta}$ chains ($96\text{ to }98\%$ in adults); Adult HbA2 has $2\text{ alpha and }2\text{ delta}$ chains ($2\text{--}4\%$ of adult Hb).

According to the polypeptide structure diagram, what chains compose fetal hemoglobin (HbF) compared to adult hemoglobin (HbA)?

Fetal HbF contains $2\text{ alpha and }2\text{ gamma}$ ($\alpha_2\gamma_2$) chains, whereas adult HbA contains $2\text{ alpha and }2\text{ beta}$ ($\alpha_2\beta_2$) chains.

Why does fetal hemoglobin (HbF) have a higher affinity for oxygen than adult hemoglobin, and when is it replaced after birth?

Higher oxygen affinity enables the extraction of $\text{O}_2$ from maternal blood; after birth, HbF is converted to HbA, a process completed by $4\text{ months}$ of age.

How does hemoglobin react with oxygen to form oxy-hemoglobin?

Oxygen attaches loosely to iron, which remains in the ferrous state ($\text{Fe}^{2+}$); this is an oxygenation reaction, not an oxidation reaction.

How does hemoglobin bind carbon dioxide to form carbamino-hemoglobin?

Carbon dioxide attaches directly to the amino groups of hemoglobin.

How does carbon monoxide interact with hemoglobin, and how does its binding affinity compare to oxygen?

Carbon monoxide attaches to iron to form carboxy-hemoglobin, preventing oxygen carriage; hemoglobin's affinity for CO is $200\text{ times}$ greater than for oxygen.

What is met-hemoglobin, what enzyme reduces it, and what disease results from congenital deficiency of that enzyme?

Met-hemoglobin is formed when strong oxidizing agents change $\text{Fe}^{2+}$ to ferric iron ($\text{Fe}^{3+}$), preventing oxygen carriage. It is normally reduced by met-hemoglobin reductase; congenital enzyme absence causes "hereditary met-hemoglobinema".

How does the buffering capacity of hemoglobin compare to that of plasma proteins?

Hemoglobin has a buffering power six times that of plasma proteins, because the amount of Hb is $16\,\text{gm/dL}$ compared to $7.3\,\text{gm/dL}$ for plasma proteins.

What are the functional advantages of the plastic biconcave shape of the red blood cell membrane?

1. Provides a larger surface area; 2. Increases flexibility so RBCs can squeeze through narrow capillaries without rupture; 3. Produces minimal increase in membrane tension when RBC volume expands in venous blood.

What two severe clinical complications occur if hemoglobin escapes RBCs and circulates free in plasma?

1. Renal failure (free Hb blocks renal tubules); 2. Increased workload on the heart (due to increased blood viscosity and colloidal osmotic pressure).

What is the normal lifespan of erythrocytes, and why do they rupture?

Lifespan is $120\text{ days} = 4\text{ months}$. Over time, glycolytic and other enzymes decline, making the cells fragile until they rupture while passing through capillaries, particularly in the spleen.

In the hemoglobin catabolism diagram, what are the breakdown products of Hb in tissue macrophages and their respective destinations?

Hemoglobin is split into Globin (recycled into the amino acid pool) and Haem. Haem is split into Iron (sent to bone marrow) and Unconjugated bilirubin (taken up by the liver and secreted as conjugated bilirubin).

What causes hemolytic jaundice in hemolytic anemia?

Increased destruction of RBCs produces large amounts of bilirubin, resulting in yellow coloration of the skin and mucous membranes.

What are the five primary physiological functions of the spleen?

1. Site of erythropoiesis during fetal life; 2. Filter that removes aged or abnormal RBCs; 3. Stores blood to release into circulation during acute hemorrhage; 4. Stores platelets; 5. Immune defense (contains lymphocytes and macrophages).

What are the clinical consequences of hypersplenism versus splenectomy?

Hypersplenism causes over-functioning of the spleen with increased destruction of blood cells. Splenectomy causes an increased risk of infections, increased RBC count, and increased platelet count (thrombocytosis).

What are the sites of erythropoiesis in the fetus, after birth, and after age 20?

Fetus: liver and spleen. After birth: bone marrow of all bones. After $20\text{ years}$: bone marrow of flat & irregular (membranous) bones (vertebrae, skull, ribs, pelvis) and the upper humerus and femur.

Based on the bone classification diagram, which types of bones maintain active marrow for erythropoiesis in individuals older than 20 years?

Flat bones (such as the sternum and ribs) and irregular bones (such as vertebrae and pelvis), along with the upper ends of long bones (humerus and femur).

Which clinical conditions produce hypoxia that stimulates erythropoiesis?

1. Lung diseases; 2. Hemorrhage (loss of RBCs); 3. Heart failure (decreased blood flow); 4. High altitude (decreased $\text{O}_2$ tension in air); 5. Athletes (relative oxygen deficiency from higher oxygen requirements).

What is the half-life and anatomical origin of erythropoietin in the fetus and in adults?

Half-life is $5\text{ hours}$. Origin in fetus: liver. Origin in adults: $85\%$ from kidneys and $15\%$ from liver (Kupffer cells / tissue macrophages).

What factors stimulate the secretion of erythropoietin?

1. Hypoxia (main stimulus; renal $\text{PO}_2$ is major factor); 2. Androgens; 3. $\beta$-adrenergic stimulants; 4. Cobalt; 5. Alkalosis at high altitudes; 6. Adenosine (inhibited by adenosine antagonists like theophylline).

Which hormones other than erythropoietin promote erythropoiesis?

Androgens, thyroid hormones, and glucocorticoids (cortisol).

What three vital roles does a healthy liver play in erythropoiesis?

1. Produces $15\%$ of erythropoietin; 2. Stores iron and vitamin $\text{B}_{12}$; 3. Synthesizes globin.

What is aplastic anemia, and what are its three major causes?

Destruction or depression of bone marrow leading to a decrease in all blood cells. Causes: 1. Radiation (X-rays, atomic); 2. Drugs (such as chloramphenicol); 3. Malignant tumours.

What dietary factors and trace elements are required for normal erythrocyte and hemoglobin synthesis?

Proteins of high biological value (build globin); Copper (cofactor for Hb formation); Cobalt (cofactor for Hb formation, component of vitamin $\text{B}_{12}$, and stimulator of erythropoietin secretion).

How do Vitamin B12 and Folic Acid compare in functions and deficiency manifestations?

Both are required for DNA synthesis and nuclear maturation (thymidine synthesis); Vitamin $\text{B}_{12}$ is additionally required for nerve myelin synthesis. Folic acid deficiency causes macrocytic anemia; $\text{B}_{12}$ deficiency causes macrocytic anemia plus neurological symptoms.

What are the daily requirements, liver storage, and absorption mechanism of Vitamin B12?

Daily requirement: $5\,\mu\text{g}$ ($5\,\text{Mg}$ in notes); liver stores: $5\,\text{mg}$. Gastric parietal cells secrete intrinsic factor which protects $\text{B}_{12}$ from GIT enzymes; it is absorbed in the terminal ileum by pinocytosis (requiring pancreatic trypsin) and carried by transcobalamin II.

What are the primary forms and percentage distributions of the 3-5 grams of iron in the human body?

$70\%$ in hemoglobin, $25\%$ as ferritin (and aggregated hemosiderin), $3\%$ in muscle myoglobin, $2\%$ in enzymes, and a small fraction bound to plasma transferrin.

What are the daily iron requirements and normal daily iron losses in adult males and females?

Daily requirement: $30\,\text{mg}$ (mostly from breakdown of Hb). Daily loss: $0.5\text{--}1.0\,\text{mg}$ in adult males and $2.0\,\text{mg}$ in adult females (due to menstrual loss).

According to the systemic iron cycle diagram, what organ serves as the main storage site containing $1000\,\text{mg}$ of iron, and how much iron is utilized daily by bone marrow for erythropoiesis?

The liver stores $1000\,\text{mg}$ of iron, and bone marrow utilizes $30\,\text{mg/day}$ for erythropoiesis.

How do dietary heme iron and non-heme iron differ in source, total intake percentage, and bioavailability?

Heme iron: from meat products, forms $10\%$ of dietary iron, high bioavailability (more absorbable). Non-heme iron: from cereals, vegetables, fruits (plant origin), forms $90\%$ of dietary iron, low bioavailability.

How are heme and non-heme iron transported across the apical membrane of duodenal enterocytes?

Heme iron is transported by heme carrier protein HCP1. Non-heme ferric iron ($\text{Fe}^{3+}$) is dissolved by gastric HCl, reduced to ferrous iron ($\text{Fe}^{2+}$) by ascorbic acid and DMT1-associated reductase, and transported via divalent metal transporter 1 (DMT1).

In the duodenal iron absorption pathway diagram, what basolateral transporter exports iron to the blood, and what ferroxidase assists it?

Iron is exported across the basolateral membrane by Ferroportin 1 and oxidized by hephaestin before binding to plasma transferrin.

What happens to absorbed iron inside the enterocyte if body stores are full versus when iron demand is high?

If stores are full, iron is stored as ferritin and lost in feces when enterocytes shed ($3\text{--}4\text{ days}$). If demand is increased, it is transported across the basolateral border via ferroportin, oxidized to $\text{Fe}^{3+}$ by ferrioxidase, and bound to transferrin (normally $35\%$ saturated).

What is hepcidin, where is it produced, and what are its physiological actions?

A $25\text{-amino acid}$ hormone secreted by the liver that degrades ferroportin. It inhibits intestinal iron absorption, iron release from macrophages, and iron release from liver stores.

How do primary polycythemia (Polycythemia Vera) and secondary polycythemia differ in etiology and cell counts?

Primary polycythemia is due to disease in RBC-forming organs, causing elevated RBCs ($6\text{--}8\text{ million/mm}^3$) as well as increased WBCs and platelets. Secondary polycythemia is caused by hypoxia (lung disease, high altitude), and WBCs and platelets remain normal.

What laboratory thresholds define anemia in males versus females?

RBC count $< 4.5\text{ million/mm}^3$ in males or $< 3.5\text{ million/mm}^3$ in females, and/or hemoglobin $< 13.5\,\text{g/dL}$ in males or $< 11.5\,\text{g/dL}$ in females.

What are the MCV and MCH characteristics of Normocytic Normochromic, Microcytic Hypochromic, and Macrocytic anemias?

Normocytic Normochromic: normal MCV, normal MCH. Microcytic Hypochromic: small MCV, decreased MCH ($<\text{normal}$). Macrocytic: larger MCV, MCH usually not increased.

What are the four primary causes of Iron Deficiency Anemia (microcytic hypochromic)?

1. Decreased intake; 2. Decreased absorption (partial gastrectomy, upper small intestine disease, vitamin C deficiency, dietary oxalates/phytic acid); 3. Increased demand (children, pregnancy, lactation); 4. Chronic blood loss (excessive menstruation, ankylostoma, peptic ulcer, piles).

What causes macrocytic (megaloblastic) anemia?

Vitamin $\text{B}_{12}$ deficiency (rarely dietary; lower ileum disease; pernicious anemia from autoimmune destruction of parietal cells; gastrectomy; liver disease) and Folic acid deficiency (decreased intake; small intestine disease; increased pregnancy demand; antifolate cytotoxic cancer drugs).

What are the structural features, count, lifespan, and origin of blood platelets?

Small, granulated, non-nucleated fragments with a normal count of $200{,}000\text{--}400{,}000/\text{mm}^3$ and a lifespan of $8\text{ days}$. Produced in bone marrow from megakaryocytes under the influence of thrombopoietin (from liver and kidneys); $30\%$ are stored in the spleen.

According to the platelet ultrastructure diagram, what specific storage granules and structural components are present inside a platelet?

Dense bodies, $\alpha$-granules, lysosomes, peroxisomes, mitochondria, glycogen, microtubules, dense tubular system, and the surface-connected canalicular system.

What are the four sequential steps of hemostasis?

1. Vasoconstriction; 2. Temporary hemostatic plug (platelet plug / primary hemostasis); 3. Definitive hemostatic plug (blood coagulation); 4. Clot dissolving (by plasmin) and vessel wall repair (by PDGF and VEGF).

What four mechanisms cause blood vessel constriction following vascular injury?

1. Nervous reflex (initiated by pain from vessel); 2. Local myogenic contraction (due to direct trauma); 3. Chemical substances from platelets (serotonin and thromboxane $\text{A}_2$); 4. Endothelin from injured endothelium.

What factors are required for platelet adhesion to injured blood vessels?

Platelets adhere to subendothelial collagen via platelet glycoprotein receptors and Von-Willebrand factor (VWF), a subendothelial and plasma glycoprotein bound to factor VIII.

What substances are released from dense granules versus alpha granules during platelet release reaction?

Dense granules release: Calcium, ADP, and Serotonin. Alpha granules release: Factor XIII, Platelet Derived Growth Factor (PDGF), Platelet Activating Factor (PAF), and Thromboxane $\text{A}_2$.

How do Thromboxane A2 and Prostacyclin (PGI2) compare in site of synthesis and biological actions?

Thromboxane $\text{A}_2$ is produced by activated platelets and causes vasoconstriction, increased release reaction, and increased platelet aggregation. Prostacyclin ($\text{PGI}_2$) is produced by endothelium and causes vasodilation, decreased release, and decreased platelet aggregation (keeps the plug localized).

Why is low-dose aspirin clinically effective in preventing myocardial infarction without completely abolishing prostacyclin?

Aspirin inhibits cyclooxygenase. Endothelial cells synthesize new cyclooxygenase enzyme to regenerate prostacyclin ($\text{PGI}_2$), whereas non-nucleated platelets cannot produce new enzyme, permanently suppressing thromboxane $\text{A}_2$.

What factors mediate platelet aggregation, fusion, and procoagulant activity?

Aggregation (loose and reversible) is mediated by ADP, $\text{TxA}_2$, PAF, and fibrinogen bridging receptors. Fusion (tight and irreversible) is caused by high ADP, thrombin, and platelet enzymes. Procoagulant activity is mediated by exposure of PF3 (platelet factor 3).

What is the biochemical nature of coagulation factors, where are they synthesized, and what are factors I, II, III, IV, XII, and XIII?

They are $13$ plasma proteins (mostly beta globulins) synthesized by the liver. Factor I: Fibrinogen; Factor II: Prothrombin; Factor III: Thromboplastin; Factor IV: Calcium; Factor XII: Glass factor; Factor XIII: Fibrin-stabilizing factor.

In the blood coagulation cascade shown in the diagram, what initial factors trigger the intrinsic pathway versus the extrinsic pathway?

The intrinsic pathway is initiated by Factor XII contact with a strange surface (assisted by prekallikrein and kininogen); the extrinsic pathway is initiated by tissue lesion releasing Factor III (tissue thromboplastin) acting with $\text{Ca}^{2+}$ on Factor VII.

How do the intrinsic and extrinsic coagulation pathways compare in speed, in vivo/in vitro occurrence, and cross-activation?

Intrinsic pathway is slow ($1\text{--}6\text{ min}$) and occurs both in vivo and in vitro; extrinsic pathway is very rapid ($15\text{ sec}$) and occurs in vivo only. Activated Factor VII (extrinsic) cross-activates Factor IX (intrinsic).

According to the cell-surface coagulation diagram, what components assemble to form the prothrombinase complex on activated platelets?

Activated Factor X (Xa), Factor Va, and prothrombin (Factor II) assembled on the membrane of an activated platelet to convert prothrombin into thrombin (IIa).

Which coagulation factors belong to the Fibrinogen group, Prothrombin group, and Contact group?

Fibrinogen group: I, V, VIII, XIII (activated by thrombin). Prothrombin group: II, VII, IX, X (require vitamin K for synthesis). Contact group: XI, XII (activated by contact with electro-negatively charged surfaces).

What is the requirement for calcium ions ($\text{Ca}^{2+}$) in the blood coagulation cascade?

Calcium is required for all steps of coagulation except the first two steps of the intrinsic pathway.

What features of healthy endothelium serve as anticlotting mechanisms?

1. Acts as a barrier preventing blood contact with collagen; 2. Smooth and negatively charged, repelling platelets and clotting factors; 3. Produces NO, prostacyclin ($\text{PGI}_2$), thrombomodulin, and tissue plasminogen activator (t-PA).

What is the active component of the fibrinolytic system, what does it produce, and what is the clinical use of recombinant t-PA?

Plasmin (fibrinolysin) lyses fibrin into fibrinogen degradation products (FDP), which inhibit thrombin. Recombinant human t-PA is administered within $6\text{ hours}$ of myocardial infarction to lyse clots in coronary arteries.

How do silicon-coated tubes, oxalates, and citrates prevent blood coagulation in vitro?

Silicon tubes prevent contact activation of Factor XII; oxalates precipitate $\text{Ca}^{2+}$ ions; citrates (used in blood transfusion bags) deionize $\text{Ca}^{2+}$ ions.

How do Heparin and Dicumarol compare regarding origin, mechanism of action, site of action, onset, duration, administration, and antidote?

Heparin: mast cells/basophils; facilitates Antithrombin III (blocks IXa, Xa, XIa, XIIa); active in vivo and in vitro; rapid onset; short duration; given by injection; antidote is Protamine sulphate $1\%$. Dicumarol: plant origin; competitive inhibition with Vitamin K in liver (blocks II, VII, IX, X); active in vivo only; slow onset; long duration; given orally; antidote is Vitamin K.

What are thrombocytopenic purpura, thrombasthenia, and vitamin K deficiency in terms of mechanism and hemostatic effects?

Thrombocytopenic purpura (platelet count $< 50{,}000/\text{mm}^3$) and thrombasthenia cause prolonged bleeding time and petechiae. Vitamin K deficiency impairs factors II, VII, IX, X and proteins C & S (caused by lack of intestinal bacteria or biliary obstruction), causing prolonged clotting time.

What are the three types of hemophilia and their missing clotting factors?

Hemophilia A ($85\%$ of cases): missing factor VIII. Hemophilia B: missing factor IX. Hemophilia C: missing factor XI. (Congenital recessive X-linked disease carried by females and manifesting in males).

What is Disseminated Intravascular Coagulation (DIC), and what clinical conditions precipitate it?

Widespread intravascular clotting caused by increased thromboplastin release from necrotic tissues, consuming clotting factors and platelets to produce severe bleeding. Causes: retention of dead fetus, septicemia, and shock.

What are the normal values and diagnostic utilities of Bleeding time, Coagulation time, Prothrombin time (PT), and Activated Partial Thromboplastin Time (APTT)?

Bleeding time: $1\text{--}3\text{ minutes}$ (platelet function, prolonged in purpura). Coagulation time: $3\text{--}10\text{ minutes}$ (prolonged in factor/liver diseases). PT: $15\text{ seconds}$ (extrinsic pathway / Factor VII, prolonged in Vit K deficiency). APTT: $30\text{--}40\text{ seconds}$ (intrinsic pathway / XII, XI, IX, VIII, prolonged in hemophilia).

In the ABO blood group system, what are the red cell antigens, plasma antibodies, and population frequencies for groups A, B, AB, and O?

Group A: Antigen A, Anti-B ($40\%$); Group B: Antigen B, Anti-A ($10\%$); Group AB: Antigens A & B, no antibodies ($5\%$, universal recipient); Group O: No antigens, Anti-A & Anti-B ($45\%$, universal donor).