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Comprehensive Pathophysiology Study Notes (Hematology, Digestive, and Urinary Systems)

Hematology: Pathophysiology and Key Concepts

  • Basic blood components

    • Most abundant protein: Albumin
    • Made by the liver
    • Most abundant blood cell: Red blood cells (RBCs)
    • Produced in the bone marrow
    • Blood cell with the shortest lifespan: Neutrophils (short-lived; many die in hours to days)

  • Hematology evaluation

    • Tests of bone marrow function
    • Blood tests
    • Large variety of tests

  • Hematology pathology terminology

    • Cytosis/-cythemia terms refer to increased cell counts
    • erythrocytosis (polycythemia)
    • leukocytosis
    • thrombocytosis (thrombocythemia)
    • Cytopenia/-penia terms refer to decreased cell counts
    • erythrocytopenia
    • leukocytopenia
    • thrombocytopenia

  • Anemia: overview

    • Anemia = HIGH RED BLOOD CELLS? (context shows “ANEMIA HIGH ow RED BLOOD CELLS”; clinically, anemia is a reduced oxygen-carrying capacity due to decreased RBC mass or hemoglobin)
    • Physiologic manifestations: reduced oxygen-carrying capacity
    • Symptoms vary with severity and compensation ability
    • Classic symptoms: fatigue, weakness, dyspnea, pallor

  • Classification of anemias by morphology and hemoglobin content

    • Based on MCV, MCH, MCHC values
    • Size terms end in -CYTIC: macrocytic, microcytic, normocytic
    • Hemoglobin content terms end in -CHROMIC: normochromic, hypochromic
    • Common combinations:
    • Macrocytic – Normochromic
    • Microcytic – Hypochromic
    • Normocytic – Normochromic

  • Major anemia categories (summary visuals)

    • Macrocytic – Normochromic: Pernicious anemia; Folate deficiency
    • Microcytic – Hypochromic: Iron deficiency anemia; Sideroblastic; Thalassemia
    • Normocytic – Normochromic: Aplastic; Posthemorrhagic; Hemolytic; Sickle cell; Anemia of chronic inflammation

  • Megaloblastic (macrocytic) anemias

    • Also termed megaloblastic anemias
    • Cause: deficiencies in vitamin B12 or folate
    • Characterized by defective DNA synthesis
    • Pernicious anemia
    • Folate deficiency anemia
    • Neurologic manifestations more common with B12 deficiency; folate deficiency typically lacks neurologic signs
    • Pernicious anemia specifics
    • Often due to lack of intrinsic factor from gastric parietal cells
    • Intrinsic factor is required for vitamin B12 absorption
    • Results in vitamin B12 deficiency
    • Typical anemia symptoms with possible neurologic manifestations (nerve demyelination)
    • Other symptoms: loss of appetite, abdominal pain, beefy red tongue (atrophic glossitis), icterus, splenic enlargement
    • Treatment: parenteral or high oral doses of vitamin B12
    • Folate deficiency specifics
    • Absorption occurs in the small intestine
    • Symptoms similar to pernicious anemia but without neurologic manifestations typically
    • Treatment: daily oral folate

  • Iron deficiency anemia (Fe deficiency)

    • Most common anemia worldwide; nutritional or metabolic/functional deficiency
    • Clinical features: brittle/rough nails, glossitis (red, sore tongue)
    • Visual cue: glossy appearance of the tongue
    • Note: iron supplementation and addressing cause are key treatments

  • Sideroblastic anemia

    • Altered mitochondrial metabolism causing ineffective iron uptake and dysfunctional hemoglobin synthesis
    • Diagnostic hallmark: ring sideroblasts in the bone marrow (erythroblasts containing iron granules not incorporated into Hb)

  • Thalassemia

    • Genetic disorder with malformed hemoglobin chains
    • Produces less hemoglobin and lowers RBC count
    • Originates in the Mediterranean region; autosomal recessive trait
    • Huge global carrier estimate (~80 million)

  • Normocytic-normochromic anemias (various causes)

    • Aplastic anemia: bone marrow failure; pancytopenia
    • Posthemorrhagic anemia: acute blood loss
    • Hemolytic anemia: accelerated destruction of RBCs; includes autoimmune etiologies
    • Sickle cell anemia: autosomal recessive; HbS causes sickling under hypoxia; loss of biconcave shape; pain crises
    • Anemia of chronic inflammation: mild-moderate anemia seen with chronic infections/inflammatory diseases (AIDS, RA, lupus, hepatitis, renal failure, cancers)

  • Pernicious anemia: deeper notes

    • Mechanism: intrinsic factor deficiency leads to B12 deficiency
    • Neurologic involvement: nerve demyelination possible
    • Other symptoms: appetite loss, abdominal pain, glossitis, icterus, splenomegaly
    • Treatment: B12 administration (parenteral or high-dose oral)

  • Vitamin B12 vs Folate: quick recall

    • B12 deficiency commonly linked to pernicious anemia and neurologic signs
    • Folate deficiency mainly affects DNA synthesis; no neurologic signs typically

  • Other key points in hematology

    • Polycythemia (excess RBCs): Absolute vs relative
    • Relative polycythemia: dehydration causing apparent increase in RBC count, Hb, Hct
    • Absolute polycythemia: abnormal stem cell proliferation (e.g., polycythemia vera) or increased erythropoietin due to hypoxia or tumors

  • Leukocyte diseases and infectious conditions

    • Infectious mononucleosis: acute EBV infection (80-85%), CMV, hepatitis, influenza, HIV
    • Splenic rupture risk is a serious complication

  • Leukemia and lymphomas (overview)

    • Leukemia: cancer with excessive accumulation of leukemic cells in marrow
    • Lymphocytic (lymphoblastic), Myeloid
    • Acute leukemia: presence of undifferentiated/immature cells (blasts)
    • Chronic leukemia: more differentiated cells present but not functioning well
    • Major types: ALL, AML, CML, CLL
    • Philadelphia chromosome: t(9;22) translocation in CML (bcr-abl fusion)
    • Lymphomas: malignant transformation of lymphocytes
    • Hodgkin lymphoma: presence of Reed–Sternberg cells
    • Non-Hodgkin lymphomas: B-cell, T-cell, NK-cell neoplasms
    • Burkitt lymphoma: fast-growing non-Hodgkin lymphoma in children; often involves EBV or HIV

  • Hemostatic disorders (brief overview)

    • Thrombocytopenia: plt count < 150,000/mm3; severe risk with counts <50k, <15k, <10k
    • Thrombocythemia: plt count > 400,000/mm3; risk of microvascular thrombosis
    • von Willebrand factor deficiency
    • Vitamin K deficiency: important for synthesis of clotting factors and anticoagulants
    • Liver disease: broad hemostatic abnormalities (coagulation, fibrinolysis, platelets)
    • Hemophilia A: factor VIII deficiency
    • Hemophilia B: factor IX deficiency (Christmas disease)
    • Disseminated intravascular coagulation (DIC): complex, high-fatality disorder with simultaneous clotting and bleeding; endothelial damage often initiates DIC; elevated FDP and D-dimer

Digestive System: Anatomy and Physiology

  • Overview of the GI tract and accessory organs

    • Main components: Mouth, Esophagus, Stomach, Small intestine (duodenum, jejunum, ileum), Large intestine (cecum, ascending, transverse, descending, sigmoid), Rectum, Anus
    • Accessory organs: Liver, Gallbladder, Pancreas, Spleen; Salivary glands (parotid, submandibular, sublingual) along with the esophagus, stomach, and intestines

  • Digestive tract layers and neural control

    • Wall layers from lumen outward: Mucosa, Submucosa, Muscularis (circular and longitudinal; stomach adds an oblique layer), Serosa
    • Enteric nervous system: Myenteric (Auerbach) plexus; Submucosal (Meissner) plexus
    • Glands: Brunner’s glands in the duodenum; various glands in mucosa/submucosa

  • Mouth, chewing, and saliva

    • Chewing and mixing with saliva; taste via CN VII and CN IX; smell via CN I
    • Saliva contents: water, mucus, electrolytes, amylase (carbohydrate digestion)
    • Paired glands: Submandibular, Sublingual, Parotid

  • Swallowing and esophagus

    • Deglutition (swallowing); peristalsis; upper and lower esophageal sphincters

  • Stomach: anatomy, secretion, and function

    • Regions and sphincters: Cardiac sphincter, Pyloric sphincter
    • Stomach walls: Fundus, Body, Pylorus
    • Secretions: Mucus, HCl acid, enzymes, hormones, intrinsic factor
    • Gastric glands and pits: Parietal cells (HCl and intrinsic factor), Chief cells (pepsinogen), G cells (gastrin), Ghrelin
    • Neural control: Vagus nerve (X) stimulates gastrin, histamine, and HCl production by Parietal cells
    • Clinical angle: full stomach removal drastically affects nutrient digestion; macro- and micronutrient absorption can be impacted

  • Duodenum and small bowel anatomy

    • Duodenal bulb; jejunum; ileum; ileocecal valve; peritoneum
    • Villi, microvilli, brush border; lacteal for fat absorption; Peyer’s patches (lymphoid tissue) in mucosa

  • Pancreas and liver/gallbladder

    • Exocrine pancreas: acini and ductal networks; enzyme and bicarbonate-rich secretions
    • Pancreatic enzymes: amylase, lipase; proteolytic zymogens (trypsinogen, chymotrypsinogen, procarboxypeptidase)
    • Pancreatic ducts secrete bicarbonate; major papilla of Vater (with bile duct) into the duodenum
    • Liver: hepatocytes produce bile; detoxification and metabolism; storage of vitamins/minerals; plasma protein synthesis; liver enzymes
    • Gallbladder: stores and concentrates bile (~90 mL capacity); bile release into duodenum via cystic and common bile ducts

  • Bile and liver physiology

    • Bile: alkaline, bile salts, cholesterol, bilirubin, electrolytes, water
    • Bilirubin: by-product of aged RBC destruction; gives bile its color and contributes to jaundice
    • Bile formation and secretion: hepatocytes → canaliculi → bile ducts
    • Liver functions: blood storage and detoxification; plasma protein and clotting factor synthesis; metabolism of fats, proteins, carbohydrates; bile production; toxin clearance; mineral/vitamin storage

Digestive Pathophysiology: Disorders of Digestion and Absorption

  • Stomach and duodenum pathology

    • Peptic Ulcer Disease (PUD): mucosal erosion/ulcers
    • Duodenal ulcers: most common PUD; often due to Helicobacter pylori, NSAIDs, hypersecretion of acid/pepsin, smoking
    • Gastric ulcers: usually in the antral region; NSAIDs, H. pylori, gastritis, alcohol
    • Esophageal ulcers: GERD; other causes include NSAIDs, smoking, vomiting (Bulimia)
    • Stress ulcers: linked to severe illness or trauma

  • Maldigestion and Malabsorption

    • Maldigestion: failure of chemical digestion
    • Malabsorption: failure of intestinal mucosa to absorb digested nutrients
    • Often occur together
    • Pancreatic insufficiency: lack of pancreatic enzymes (lipase, amylase) and bicarbonate; causes fat maldigestion → fatty stools and weight loss; may accompany pancreatitis or pancreatic cancer
    • Lactase deficiency: lactose intolerance; fermentation by bacteria → gas, cramps, osmotic diarrhea
    • Bile salt deficiency: impaired fat emulsification/absorption; fat-soluble vitamin deficiencies (A, D, E, K)
    • Fat-soluble vitamin deficiencies: A (night blindness, xerosis), D (bone disease), E (neurological issues), K (coagulation defects)

  • Vitamins and deficiency signs

    • Vitamin A: night blindness, xerophthalmia
    • Vitamin D: rickets (children), osteomalacia (adults)
    • Vitamin K: prolonged prothrombin time, purpura, petechiae
    • Vitamin E: neurologic symptoms possible (oxidative protection roles)
    • General PEM (protein-energy malnutrition): Kwashiorkor (edema, stunted growth) vs Marasmus (severe wasting); cachexia as a broader term

  • Gallbladder and biliary disorders

    • Cholelithiasis (gallstones): cholesterol stones most common; pigmented stones with cirrhosis
    • Cholecystitis: gallbladder inflammation

  • Liver disease spectrum

    • Hepatitis A, B, C: viral hepatitis with varying transmission (A-fecal–oral; B/HBV via blood/body fluids; C via transfusions/IV drug use)
    • Cirrhosis: irreversible inflammatory liver disease; nodular/fibrotic tissue; portal hypertension; potential hepatic encephalopathy
    • Alcoholic liver disease; Biliary disease; Fatty liver disease (NAFLD/NASH)
    • Portal hypertension consequences: esophageal varices, splenomegaly, ascites, hepatic encephalopathy
    • Jaundice: due to bilirubin metabolism failure; prehepatic, hepatic, or posthepatic causes
    • Pancreatitis: inflammation of pancreas; autodigestion by activated pancreatic enzymes; can become chronic with alcohol use

  • Obesity and eating disorders

    • Obesity: BMI ≥ 30; health risks and societal implications; male vs female fat distribution differences (visceral vs subcutaneous fat)
    • Anorexia nervosa: extreme food restriction; distorted body image; possible lanugo; briefer features include lanugo, xerosis, hair/skin changes; risk of cardiac failure in severe cases
    • Bulimia nervosa: normal or near-normal weight with binge-purge cycles; dental erosion, pharyngoesophageal inflammation; Russell’s sign (knuckle scarring from induced vomiting); laxative abuse risks
    • Body dysmorphia and societal pressures

  • Nutrition-related disorders and GI cancers risk

    • Malnutrition and PEM; Kwashiorkor vs Marasmus; cachexia
    • Crohn’s disease vs Ulcerative Colitis
    • Crohn’s: idiopathic inflammatory bowel disease; any GI tract segment; skip lesions; cobblestone appearance
    • Ulcerative Colitis: continuous mucosal inflammation of the colon; increased colon cancer risk
    • Diverticular disease of the colon: diverticulosis vs diverticulitis; herniation through colon wall; sigmoid colon commonly involved
    • Appendicitis: inflammation of the vermiform appendix; physical signs (rebound tenderness, McBurney’s point, Rovsing’s sign, psoas/obturator signs); WBC elevation; imaging

  • Motility and mechanical disorders

    • Abdominal hernias: umbilical, incisional, inguinal, abdominal wall defects
    • Pyloric obstruction: blockage between stomach and duodenum
    • Dumping syndrome: rapid gastric emptying after partial gastrectomy/pyloroplasty; GI symptoms due to osmotic shift
    • Intestinal obstruction: mechanical blockage or ileus (loss of peristalsis)
    • Volvulus and intussusception: mechanical causes of obstruction

  • Gastrointestinal nutrition and absorption highlights

    • Duodenum: iron, water, calcium absorption
    • Jejunum: sugars, proteins
    • Ileum: sugars, bile salts, vitamin B12 (requires intrinsic factor)
    • Large intestine: water and electrolyte absorption
    • Absorption of vitamins and minerals across intestinal mucosa; role of bile acids in fat digestion

Urinary System: Anatomy and Physiology

  • Anatomy overview

    • Kidneys, ureters, bladder, urethra
    • Retroperitoneal location; renal vessels and peritoneum relationships

  • Renal physiology: key processes

    • Renal function: filtration, reabsorption, secretion
    • Regulation of urine volume: RAAS, ADH (arginine vasopressin), natriuretic peptides (ANP, etc.)

  • Glomerular filtration and the filtration barrier

    • Glomerular filtration membrane components: capillary endothelium, basement membrane, visceral and parietal walls with filtration slits
    • Filtration process: movement of water and protein-free solutes from plasma across the glomerular capsule into Bowman’s space to form filtrate (primary urine)
    • Filtration pressure dynamics (net filtration pressure, NFP)

  • Key pressures in filtration (example numbers)

    • Example: Glomerular hydrostatic pressure HP_gc = 55 mm Hg
    • Capsular hydrostatic pressure HP_cs = 15 mm Hg
    • Glomerular osmotic pressure OP_gc = 30 mm Hg
    • Net filtration pressure:
      ext{NFP} = HP{gc} - (HP{cs} + OP_{gc})
      ext{NFP} = 55 - (15 + 30) = 10 ext{ mmHg}

  • GFR: Glomerular Filtration Rate

    • Definition: rate of movement of fluid out of the glomerulus into Bowman’s space
    • GFR is directly proportional to NFP:
      ext{GFR} \propto \text{NFP}
    • GFR can be modulated by vasodilation/vasoconstriction of afferent/efferent arterioles and systemic blood pressure

  • Flow of filtrate and blood in the nephron

    • Flow path: Afferent arteriole → Glomerulus → Efferent arteriole → Peritubular capillaries
    • Filtrate moves from glomerulus into Bowman’s capsule and through the nephron tubules

  • Nephron and juxtaglomerular apparatus (JGA)

    • Functional unit: nephron (~1.2 million per kidney)
    • Components: proximal tubule, loop of Henle (descending and ascending limbs), distal tubule, collecting duct
    • Juxtaglomerular apparatus: macula densa monitory Na+ and flow; juxtaglomerular cells release renin
    • Macula densa senses NaCl; renin release from JG cells responds to changes in perfusion pressure

  • Nephron processes: filtration, reabsorption, secretion

    • Filtration: movement of water and solutes into Bowman's capsule
    • Reabsorption: movement of ions, water, glucose, amino acids from tubule back to blood
    • Major reabsorbed ions: Na+, Cl−, HCO3−, K+, Ca2+; water follows osmotically
    • Key sites: proximal tubule (most reabsorption), loop of Henle (countercurrent mechanism for concentration), distal tubule/collecting duct (aldosterone/ADH regulated)
    • Example transporter overview (illustrative): Na+ and water reabsorption driven by transporters and gradients; negative ions attracted to positive ions; osmotic effects drive water movement
    • Secretion: movement of substances from peritubular blood/renal tissue into tubule for excretion
    • Substances: H+, HCO3−, K+, NH3/NH4+, urea; various drugs and toxins

  • Hormonal and regulatory controls of renal function

    • RAAS (Renin-Angiotensin-Aldosterone System): pivotal for Na+ and water reabsorption and BP control
    • Renin released by juxtaglomerular cells; converts angiotensinogen (liver) to angiotensin I; ACE (lungs) converts to angiotensin II
    • Angiotensin II effects: vasoconstriction of efferent arteriole, stimulates aldosterone secretion, stimulates ADH, increases thirst
    • Pathway (simplified):
      \text{Renin} + \text{Angiotensinogen} \rightarrow \text{Angiotensin I} \xrightarrow{\text{ACE}} \text{Angiotensin II}
    • Aldosterone: increases Na+ reabsorption in distal tubule and collecting duct; promotes K+ secretion
    • Antidiuretic hormone (ADH/vasopressin): increases water reabsorption in collecting ducts via aquaporin channels
    • Natriuretic peptides (ANP, etc.): promote Na+ and water excretion (opposite of RAAS)
    • Other regulators: urodilatin, vitamin D metabolism for Ca2+ absorption, erythropoietin production with hypoxia
    • Renin-angiotensin-aldosterone system (RAAS) map highlights how ↑ Aldosterone → ↑ Na+ reabsorption → ↑ water reabsorption → ↑ Blood volume → ↑ Cardiac output

  • Concentration and dilution of urine

    • Urine concentration depends on ADH and the osmolarity gradient in the medulla (countercurrent mechanism)
    • Urea, aldosterone, and natriuretic peptides influence final urine tonicity

  • Lab markers for kidney function

    • Creatinine clearance and glomerular filtration rate (GFR)
    • Blood tests: plasma creatinine; blood urea nitrogen (BUN)

  • Quick reference: flow and function recap

    • Filtration: plasma to filtrate at glomerulus ( Bowman's capsule )
    • Reabsorption: tubules return essential solutes and water to blood
    • Secretion: waste and toxins moved into tubule
    • Net effect: regulate volume, composition, and pH of body fluids

Key Connections and Real-World Relevance

  • Linking hematology and nutrition
    • Iron, B12, and folate status directly shape RBC production and morphology
    • Nutritional deficiencies manifest as specific anemia patterns (microcytic, macrocytic, normocytic)
  • GI physiology underpins nutrient absorption and metabolism affecting systemic health (anemia risk, bone health, immune function)
  • Renal physiology is central to BP regulation, electrolyte balance, acid-base homeostasis, and toxin clearance; dysregulation contributes to edema, hypertension, and metabolic disorders
  • Obesity, eating disorders, and metabolic syndrome have broad systemic impacts including liver, GI, and renal function; integrating GI physiology with nutrition helps explain disease mechanisms

Equations and Formulas (LaTeX)

  • Net Filtration Pressure (NFP) in the glomerulus:
    \text{NFP} = HP{gc} - (HP{cs} + OP_{gc})
  • Example value set and calculation:
    HP{gc} = 55\;\text{mm Hg}, \quad HP{cs} = 15\;\text{mm Hg}, \quad OP_{gc} = 30\;\text{mm Hg}
    \text{NFP} = 55 - (15 + 30) = 10\;\text{mm Hg}
  • Glomerular Filtration Rate (GFR) relationship:
    \text{GFR} \propto \text{NFP}
  • RAAS cascade (schematic):
    \text{Renin} + \text{Angiotensinogen} \rightarrow \text{Angiotensin I} \xrightarrow{\text{ACE}} \text{Angiotensin II}

Note: Where relevant, diagnostic and clinical decision points (e.g., thresholds for thrombocytopenia, levels of bilirubin in jaundice, or typical causes of ulcers) are included in the sections above for quick recall.

Quick Reference: Major Conditions and Key Features

  • Pernicious anemia: B12 deficiency due to intrinsic factor loss; neurologic signs; treat with B12
  • Folate deficiency: similar anemia signs but no neuro symptoms typically; treat with folate
  • Iron deficiency anemia: glossitis; most common worldwide; treat with iron supplementation
  • Sideroblastic anemia: ring sideroblasts; mitochondrial iron mishandling
  • Thalassemia: Mediterranean origin; autosomal recessive; reduced Hb; carrier prevalence high
  • Sickle cell disease: HbS mutation; HbS polymerization under hypoxia; vaso-occlusive crises
  • Leukemias and Lymphomas: various types with characteristic cellular findings; Philadelphia chromosome in CML; RS cells in HL; Burkitt's in children
  • Coagulation disorders: DIC, Hemophilia A/B, von Willebrand disease, liver disease–associated coagulopathies
  • Peptic ulcers and PUD: H. pylori, NSAIDs, smoking; duodenal ulcers most common
  • Inflammation-related GI diseases: Crohn’s disease (skip lesions, cobblestone); Ulcerative colitis (colonic mucosa); increased colon cancer risk in UC
  • Obesity and eating disorders: BMI-based classifications; physical and psychological health impacts; dental and GI consequences of bulimia
  • Portal hypertension: varices, splenomegaly, ascites, hepatic encephalopathy
  • Hepatitis and cirrhosis: viral etiologies; progressive liver failure and its systemic effects
  • Pancreatitis: autodigestion by activated enzymes; cholestasis and metabolic consequences
  • Renal physiology basics: filtration, reabsorption, secretion; RAAS and ADH as primary regulators; GFR and creatinine as functional markers