Nursing(Degree) · First Year · NUR101
Anatomy and Physiology
Anatomy and Physiology is one of the most important foundation courses for nursing students in Zambia. This course helps you understand how the human body is structured and how it functions, from major organs to body systems such as the nervous, cardiovascular, respiratory, and digestive …
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Anatomy and Physiology is one of the most important foundation courses for nursing students in Zambia. This course helps you understand how the human body is structured and how it functions, from major organs to body systems such as the nervous, cardiovascular, respiratory, and digestive systems. A strong grasp of this subject is essential for exams set by nursing schools and regulatory bodies in Zambia. At 25schools, we simplify complex anatomy concepts using exam-focused questions, diagrams, and clear explanations designed for nursing exams. Whether you are preparing for tests, assignments, or final examinations, this course builds the clinical understanding every successful nurse needs. Start studying with 25schools today and gain the confidence to excel in anatomy and physiology exams.
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Topic 181Coming soon
Polyarteritis Nodosa
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized arteries, sparing small vessels (capillaries, venules). Therefore, PAN does NOT cause glomerulonephritis or pulmonary capillaritis. For Zambian students, PAN is a critical diagnosis associated with HEPATITIS B VIRUS (HBV) infection (10-30% of cases), which is endemic in Zambia. Pathophysiology: necrotizing inflammation of muscular arteries → fibrinoid necrosis, aneurysmal dilation (microaneurysms), thrombosis, ischemia, infarction. HBV-associated: immune complex deposition (HBsAg, anti-HBs). Clinical: CONSTITUTIONAL (90%)—fever, weight loss, malaise. NEUROLOGIC (50-80%)—MONONEURITIS MULTIPLEX (wrist drop, foot drop), peripheral neuropathy (asymmetric, painful), stroke. RENAL (60-80%)—renal artery vasculitis → RENAL INFARCTION (flank pain, hematuria), HYPERTENSION (renin-mediated), progressive renal failure. NO GLOMERULONEPHRITIS (no RBC casts, proteinuria minimal). CUTANEOUS (40-60%)—livedo reticularis, nodules, ulcers, digital gangrene. GASTROINTESTINAL (30-50%)—mesenteric ischemia: post-prandial abdominal pain, weight loss, GI bleeding, perforation, infarction (surgical emergency). CARDIAC (20-30%)—myocardial infarction (coronary arteritis), heart failure. TESTICULAR (20-30%)—orchitis, testicular pain. MUSCULOSKELETAL (50-70%)—arthralgia, myalgia. HBV-ASSOCIATED PAN: more severe, periarterial nodules (pathognomonic). Diagnosis: CLINICAL + BIOPSY + ANGIOGRAPHY. BIOPSY (nerve, muscle, skin, testis, liver): necrotizing arteritis, fibrinoid necrosis, transmural inflammation. ANGIOGRAPHY (conventional, CT, MR): MICROANEURYSMS (1-5mm), beading, stenosis of medium visceral arteries (renal, mesenteric, hepatic)—highly suggestive, not specific. LAB: elevated ESR/CRP, leukocytosis, anemia, thrombocytosis, elevated LFTs (HBV), HBsAg+ (10-30%), ANCA NEGATIVE (crucial distinction from MPA). Management: NON-HBV PAN: CORTICOSTEROIDS (prednisone 1 mg/kg/day) + CYCLOPHOSPHAMIDE (IV pulse or oral) for severe (renal, GI, cardiac, CNS). MILD (skin, joints, mild neuropathy): corticosteroids alone ± methotrexate/azathioprine. HBV-ASSOCIATED PAN: TREAT HBV (antivirals: lamivudine, entecavir, tenofovir) + SHORT COURSE CORTICOSTEROIDS + PLASMA EXCHANGE (removes immune complexes). Cyclophosphamide AVOIDED (prolonged immunosuppression in HBV). Prognosis: Without treatment, 5-year survival <20%. With modern therapy, 5-year survival 80-90%. Relapse rate 10-20%. Zambian context: PAN is associated with HBV (high prevalence). Think PAN in patient with: MONONEURITIS MULTIPLEX + HYPERTENSION + RENAL INFARCT + MICROANEURYSMS + HBsAg+. NO GLOMERULONEPHRITIS. Renal biopsy NOT diagnostic (spares glomeruli). Angiography (CT, MR) accessible tertiary centres. Cyclophosphamide, corticosteroids accessible. Antivirals (tenofovir) accessible. Plasma exchange limited. Biopsy (sural nerve, muscle, skin) accessible. High index suspicion.
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IgG4-Related Disease
IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by tumor-like swelling of involved organs, dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis, and frequently elevated serum IgG4 concentrations. For Zambian students, recognition is emerging; IgG4-RD mimics malignancy, infection, and other inflammatory diseases—diagnosis prevents unnecessary surgery, enables dramatic steroid response. Pathophysiology: unknown; autoimmune, allergic? Genetic (HLA). CD4+ cytotoxic T cells, plasmablasts secrete IL-1β, TGF-β, IFN-γ → fibrosis. IgG4 itself not pathogenic. Clinical: SUBACUTE, PROGRESSIVE enlargement of one or multiple organs, often mistaken for cancer. TYPE 1 AUTOIMMUNE PANCREATITIS (AIP, 60%)—diffuse/focal pancreatic enlargement, capsule-like rim, irregular main pancreatic duct (strictures, pre-stenotic dilation), obstructive jaundice (painless), diabetes, exocrine insufficiency. SCLEROSING CHOLANGITIS—bile duct strictures (intrahepatic, extrahepatic), mimics primary sclerosing cholangitis (PSC), but responds to steroids. SIALADENITIS—bilateral, symmetric, chronic enlargement of SUBMANDIBULAR GLANDS > parotid, lacrimal (Mikulicz syndrome—distinct from Sjögren's: no anti-Ro/La, male predominance, steroid-responsive). ORBITAL—lacrimal gland enlargement, extraocular muscle enlargement, infraorbital nerve enlargement, proptosis. RETROPERITONEAL FIBROSIS—perianeurysmal/periaortitis, ureteral obstruction, hydronephrosis, renal impairment. THYROID—RIEDEL THYROIDITIS (fibrous replacement, rock-hard goiter, tracheal/esophageal compression, hypothyroidism). LYMPHADENOPATHY—generalized, often cervical, mediastinal, axillary. RENAL—tubulointerstitial nephritis (hypocomplementemic), membranous nephropathy. PULMONARY—inflammatory pseudotumor, interstitial pneumonia, pleural thickening. Diagnosis: HISTOPATHOLOGY—essential for definitive diagnosis. Characteristic triad: DENSE LYMPHOPLASMACYTIC INFILTRATE, STORIFORM FIBROSIS (cartwheel pattern), OBLITERATIVE PHLEBITIS (vein occlusion by inflammatory infiltrate). IgG4+ plasma cells >10/HPF, IgG4/IgG ratio >40%. SERUM IgG4—elevated (>135 mg/dL) in 70% (not specific, not required). Elevated IgE, eosinophilia (30%). Hypocomplementemia (renal). IMAGING: CT/MRI—diffuse/focal organ enlargement, delayed enhancement, capsule-like rim (pancreas), soft tissue rind around aorta (retroperitoneal fibrosis). PET-CT—increased FDG uptake, assess disease extent, guide biopsy. Management: GLUCOCORTICOIDS—first-line; dramatic, rapid response is characteristic (confirmatory). Prednisone 0.6 mg/kg/day x 2-4 weeks, taper over 3-6 months. Relapse common (30-50%) during taper. STEROID-SPARING: methotrexate, azathioprine, mycophenolate, rituximab (highly effective, B-cell depletion). RETROPERITONEAL FIBROSIS: ureteral stenting/nephrostomy, surgical ureterolysis (refractory). BILIARY: ERCP, stenting. Prognosis: excellent response to steroids; chronic relapsing course. Long-term sequelae: irreversible fibrosis (cirrhosis, bile duct obliteration, renal atrophy), increased malignancy risk (lymphoma). Zambian context: emerging recognition, likely underdiagnosed. Consider in: unexplained pancreatic mass (not cancer), bilateral submandibular/lacrimal enlargement (not Sjögren's), retroperitoneal fibrosis with hydronephrosis, Riedel thyroiditis. Biopsy essential; pathology services require IgG4 immunohistochemistry. Serum IgG4 limited availability. Corticosteroids accessible, dramatically effective. Rituximab unavailable.
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Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a chronic, progressive, autoimmune cholestatic liver disease characterized by destruction of small-to-medium-sized intrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and liver failure. For Zambian students, PBC is a key differential diagnosis in middle-aged women presenting with unexplained fatigue, pruritus, and elevated alkaline phosphatase. Pathophysiology: autoimmune-mediated, T-cell lymphocytic infiltration and destruction of biliary epithelial cells (cholangiocytes) in interlobular bile ducts. Antimitochondrial antibodies (AMA) are present in 95%, targeting the E2 subunit of pyruvate dehydrogenase complex (PDC-E2). Genetic susceptibility (HLA-DR8, DR11). Environmental triggers (infection, xenobiotics). Progressive ductopenia → chronic cholestasis → hepatotoxic bile acid accumulation → fibrosis, cirrhosis. Clinical: FEMALE PREDOMINANCE (9:1), peak age 40-60 years. ASYMPTOMATIC (20-60%)—incidental finding of elevated ALP. FATIGUE (50-80%)—most common symptom, debilitating, not correlated with liver disease severity. PRURITUS (50-70%)—often worse at night, palms, soles, may precede jaundice by years. RIGHT UPPER QUADRANT PAIN (10-20%). JAUNDICE (late sign). COMPLICATIONS OF CIRRHOSIS/CHOLESTASIS: portal hypertension (ascites, variceal hemorrhage), synthetic dysfunction, hypercholesterolaemia (xanthelasma, xanthomas), fat-soluble vitamin deficiency (A, D, E, K), steatorrhoea, metabolic bone disease (osteoporosis, osteomalacia), hypothyroidism (20%), sicca syndrome (Sjögren's overlap, 30-50%), Raynaud's, CREST syndrome. Diagnosis: CHOLESTATIC LIVER BIOCHEMISTRY—elevated ALP, GGT; ALT/AST mildly elevated (early). SERUM AMA POSITIVE (titre ≥1:40)—95% sensitive, 98% specific. AMA-NEGATIVE PBC (5%)—requires liver biopsy for diagnosis. LIVER BIOPSY—indicated if AMA-negative, suspected overlap syndrome (AIH), or atypical features. Histology: florid duct lesion (nonsuppurative destructive cholangitis), granulomatous bile duct destruction, lymphocytic infiltration, ductopenia. STAGING: I—portal inflammation, II—periportal fibrosis, III—septal fibrosis, IV—cirrhosis. IMAGING (ultrasound, MRCP)—excludes biliary obstruction, secondary cholangitis. OTHER LAB: elevated IgM (polyclonal), hypercholesterolaemia (HDL), elevated AMA subtyping (M2), elevated transaminases (overlap). SCREENING: thyroid function (hypothyroidism), vitamin D, bone density (osteoporosis). Management: URSODEOXYCHOLIC ACID (UDCA) 13-15 mg/kg/day—FIRST-LINE THERAPY. Improves liver biochemistries, delays histologic progression, improves transplant-free survival. Response assessed at 1 year (Paris I/II, Barcelona, Rotterdam criteria). OBETICHOLIC ACID (FXR agonist)—SECOND-LINE for inadequate response to UDCA. Fibrates (bezafibrate, fenofibrate)—off-label, improves ALP. PRURITUS: cholestyramine (bile acid sequestrant, give 4h apart from other meds), rifampicin, naltrexone, sertraline. FATIGUE: no effective pharmacotherapy; treat contributing factors (anaemia, hypothyroidism, sleep disturbance, depression). CIRRHOSIS COMPLICATIONS: screen for varices (upper endoscopy), treat osteoporosis (calcium, vitamin D, bisphosphonates), fat-soluble vitamin supplementation. LIVER TRANSPLANTATION: indicated for decompensated cirrhosis, intractable pruritus, HCC. PBC recurs in 20-30% post-transplant. Prognosis: With UDCA therapy, most patients have normal life expectancy. Poor prognosis: inadequate biochemical response to UDCA, advanced histologic stage at diagnosis, young age at diagnosis. GLOBE and UK-PBC scores predict transplant-free survival. Zambian context: PBC is underrecognized. Think PBC in middle-aged woman with: 1) UNEXPLAINED ELEVATED ALP (with GGT), 2) FATIGUE, PRURITUS, 3) AMA POSITIVE. AMA testing available (University Teaching Hospital, Lusaka). UDCA available (expensive, but essential). Cholestyramine, rifampicin, naltrexone, sertraline for pruritus—variable availability. Bone health management (calcium, vitamin D, bisphosphonates). Overlap with AIH (10-20%)—requires corticosteroids + UDCA. Transplant unavailable. Early diagnosis, UDCA therapy, and monitoring for cirrhosis complications is key.
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Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease characterized by diffuse inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts, leading to multifocal bile duct strictures, cholestasis, cirrhosis, and an increased risk of cholangiocarcinoma and colorectal cancer. For Zambian students, PSC is strongly associated with INFLAMMATORY BOWEL DISEASE (IBD, particularly ulcerative colitis, 70-80%), which is less common in Africa but increasingly recognized. Pathophysiology: unknown, likely autoimmune/genetic (HLA-B8, DR3, DR52a), bile duct injury → periductal fibrosis, concentric 'onion-skin' fibrosis, obliterative cholangitis → multifocal strictures, prestenotic dilation, cholestasis, biliary cirrhosis. Clinical: MALE PREDOMINANCE (2:1), peak age 30-40 years. ASYMPTOMATIC (15-40%)—incidental elevated ALP. FATIGUE, PRURITUS (70%). RIGHT UPPER QUADRANT PAIN, FEVER (acute cholangitis—bacterial superinfection of obstructed ducts). JAUNDICE (intermittent, progressive). COMPLICATIONS: DOMINANT STRICTURE (high-grade biliary obstruction, 50%), CHOLANGIOCARCINOMA (10-15% lifetime risk—annual surveillance), GALLBLADDER POLYPS/MASS (40-60% malignant), COLORECTAL CANCER (IBD-associated, 5-fold risk, annual colonoscopy), PORTAL HYPERTENSION, CIRRHOSIS, CHOLESTEATOSIS, FAT-SOLUBLE VITAMIN DEFICIENCY, METABOLIC BONE DISEASE. IBD: 70-80% have UC (pancolitis, rectal sparing, backwash ileitis), 5-10% Crohn's. IBD may precede PSC, present concurrently, or develop years after liver transplant. Diagnosis: CHOLESTATIC LIVER BIOCHEMISTRY—elevated ALP, GGT; ALT/AST variable. AMA NEGATIVE (95%). p-ANCA positive (30-80%, not specific). IMAGING: MRCP is diagnostic—MULTIFOCAL, SHORT, ANNULAR STRICTURES ALTERNATING WITH NORMAL OR DILATED SEGMENTS—'BEADED' APPEARANCE. Intrahepatic and extrahepatic ducts. ERCP: diagnostic and therapeutic (stricture dilation, stenting). LIVER BIOPSY: not required for diagnosis if classic imaging; may show periductal 'onion-skin' fibrosis, ductopenia, biliary cirrhosis. Overlap with AIH (PSC-AIH overlap, 5-10%)—children, young adults. Management: NO CURATIVE MEDICAL THERAPY. UDCA (15-20 mg/kg/day) improves LFTs, no proven survival benefit, may increase colorectal adenoma risk (high-dose). NOT RECOMMENDED routinely. DOMINANT STRICTURE: ERCP WITH DILATION/STENTING—improves cholestasis, reduces cholangitis risk. CHOLANGITIS: antibiotics (ciprofloxacin, metronidazole). PRURITUS: cholestyramine, rifampicin, naltrexone, sertraline. FAT-SOLUBLE VITAMIN DEFICIENCY: supplementation (A, D, E, K). METABOLIC BONE DISEASE: calcium, vitamin D, bisphosphonates. IBD: mesalamine, immunomodulators, biologics. COLON CANCER SURVEILLANCE: colonoscopy q1-2 years starting at diagnosis of PSC. CHOLANGIOCARCINOMA SURVEILLANCE: annual MRCP/ERCP + CA19-9 (suboptimal sensitivity/specificity); no proven survival benefit. LIVER TRANSPLANTATION: indicated for decompensated cirrhosis, refractory pruritus, recurrent cholangitis, cholangiocarcinoma (early, protocol). PSC recurs in 20-30% post-transplant. Prognosis: variable; median transplant-free survival 12-18 years from diagnosis. Poor prognosis: older age, jaundice at diagnosis, elevated bilirubin, advanced histologic stage, dominant stricture, cholangiocarcinoma. Zambian context: PSC is RARE in sub-Saharan Africa (parallels IBD incidence). However, with increasing urbanization and diagnosis of IBD, PSC will be encountered. Consider PSC in young/middle-aged patient with: 1) CHOLESTATIC LIVER BIOCHEMISTRY, 2) IBD (UC), 3) MRCP showing BEADED DUCTS. AMA negative. UDCA expensive, not routinely recommended. ERCP available tertiary centres (Lusaka). Cholangiocarcinoma surveillance challenging. Liver transplant unavailable. IBD management: mesalamine, sulfasalazine accessible; biologics unavailable. High index suspicion, multidisciplinary care (gastroenterology, radiology, surgery).
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Topic 185Coming soon
Autoimmune Hepatitis
Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease of unknown etiology, characterized by interface hepatitis, hypergammaglobulinaemia, and circulating autoantibodies. It is highly responsive to immunosuppressive therapy. For Zambian students, AIH is a critical diagnosis—it is often misdiagnosed as viral hepatitis (which is endemic) or cirrhosis of unknown cause, yet it is TREATABLE and, if untreated, PROGRESSES TO CIRRHOSIS AND LIVER FAILURE. Pathophysiology: loss of immune tolerance to hepatocyte autoantigens (asialoglycoprotein receptor, CYP2D6, etc.) in genetically susceptible individuals (HLA-DR3, DR4) → T-cell-mediated hepatocyte apoptosis, necrosis, interface hepatitis. Environmental triggers (infection, drugs). Classification: TYPE 1 AIH (80%)—ANA and/or SMA positive, any age, female predominance. TYPE 2 AIH (10-20%)—anti-LKM1 positive, children/young adults, more severe, often presents as acute hepatitis. Clinical: INSIDIOUS ONSET (50-70%)—fatigue, malaise, anorexia, nausea, right upper quadrant pain, arthralgia, myalgia. ACUTE HEPATITIS (30-50%)—jaundice, dark urine, pale stools, fever, tender hepatomegaly—may mimic acute viral hepatitis. CIRRHOSIS (30%) at presentation—signs of portal hypertension (ascites, variceal hemorrhage, splenomegaly). ASYMPTOMATIC (10-20%)—incidental elevated LFTs. EXTRAHEPATIC (20-50%)—arthralgia, Sjögren's, thyroiditis, UC, SLE, RA, CREST. Diagnosis: ELEVATED TRANSAMINASES (AST, ALT)—variable, may be >1000 IU/L in acute flares. ELEVATED IgG (polyclonal) or TOTAL GLOBULIN. AUTOANTIBODIES: TYPE 1: ANA (+) 60-80%, SMA (+) 60-80%; TYPE 2: anti-LKM1 (+) 100%. LIVER BIOPSY ESSENTIAL for diagnosis—INTERFACE HEPATITIS (piecemeal necrosis), lymphoplasmacytic infiltrate (portal and periportal), emperipolesis, hepatocyte rosettes. Fibrosis, cirrhosis (late). EXCLUSION of viral hepatitis (A, B, C, E), Wilson's disease, drug-induced liver injury, alcohol, NASH, PBC/PSC overlap. DIAGNOSTIC SCORING: Revised IAIHG score (research), Simplified IAIHG score (clinical). Management: IMMUNOSUPPRESSION INDICATED for: ALT >10x ULN, ALT >5x ULN + IgG >2x ULN, bridging necrosis/multilobular collapse on biopsy, or symptomatic disease. FIRST-LINE: CORTICOSTEROIDS—prednisone (or prednisolone) 0.5-1 mg/kg/day (max 40-60 mg/day) + AZATHIOPRINE (1-2 mg/kg/day) for steroid-sparing, reduced relapse. Prednisone monotherapy: if azathioprine contraindicated (TPMT deficiency, cytopenia). TAPER: 2-4 weeks after response (normalization ALT, IgG), slow taper over 12-24 months. SECOND-LINE: mycophenolate mofetil (intolerant to azathioprine), tacrolimus, cyclosporine, rituximab, infliximab (refractory). LIVER TRANSPLANTATION: decompensated cirrhosis, acute liver failure unresponsive to steroids. AIH recurs in 20-30% post-transplant. Prognosis: REMISSION achieved in 80% with treatment, within 3-6 months. RELAPSE common (50-80%) after treatment withdrawal—most require long-term low-dose immunosuppression. WITHOUT TREATMENT, 5-year mortality 50%, 10-year mortality 90%. TREATMENT IMPROVES SURVIVAL TO >90% at 10 years. Zambian context: AIH IS UNDERDIAGNOSED. Think AIH in patient with: 1) PERSISTENTLY ELEVATED AMINOTRANSFERASES (AST/ALT) without viral hepatitis (HBsAg, anti-HCV negative), 2) HYPERGAMMAGLOBULINAEMIA (elevated total protein, IgG), 3) POSITIVE AUTOANTIBODIES (ANA, SMA, anti-LKM1). ANA, SMA testing available (University Teaching Hospital). Anti-LKM1 testing limited. Liver biopsy accessible tertiary centres. Corticosteroids (prednisone) and azathioprine are ACCESSIBLE and INEXPENSIVE. Mycophenolate available. Rituximab, infliximab, tacrolimus unavailable. EXCLUDE Wilson's disease (ceruloplasmin, slit-lamp) in young patients. TREAT EARLY, TREAT AGGRESSIVELY. Long-term monitoring for medication toxicity, osteoporosis, metabolic complications of steroids. Patient education: AIH is CHRONIC, requires LONG-TERM immunosuppression, NON-ADHERENCE CAUSES RELAPSE, PROGRESSION TO CIRRHOSIS. TRANSFERRED TO TERTIARY CENTRE (hepatology) for biopsy and initiation of therapy.
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Topic 186Coming soon
IgG4-Related Sclerosing Cholangitis
IgG4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of IgG4-related disease (IgG4-RD), characterized by bile duct strictures, cholestasis, and dramatic response to corticosteroids. It is a critical DIFFERENTIAL DIAGNOSIS OF PRIMARY SCLEROSING CHOLANGITIS (PSC) and PANCREATIC/BILLIARY MALIGNANCY. For Zambian students, recognition is essential—IgG4-SC is STEROID-RESPONSIVE, whereas PSC and malignancy are not. Pathophysiology: dense lymphoplasmacytic infiltration of bile duct walls with abundant IgG4+ plasma cells, storiform fibrosis, obliterative phlebitis. Often associated with AUTOIMMUNE PANCREATITIS (AIP, 60-80%). Clinical: CHOLESTATIC JAUNDICE (70-80%)—painless, progressive. ABDOMINAL PAIN (30-40%). WEIGHT LOSS (30-50%). TYPE 1 AIP (90%): diffuse pancreatic enlargement, capsule-like rim. Type 2 AIP (10%): idiopathic duct-centric pancreatitis, no IgG4 elevation, no systemic involvement. DISTINGUISHING IgG4-SC from PSC: IgG4-SC—Older age (60-70y vs 30-40y), acute/subacute presentation, obstructive jaundice, weight loss, associated pancreatitis, NO IBD (PSC: 70-80% UC), response to steroids. PSC—Younger age, male predominance, chronic course, IBD association (70-80%), asymptomatic or fatigue/pruritus, beaded ducts, NO steroid response. DISTINGUISHING IgG4-SC from CHOLANGIOCARCINOMA: IgG4-SC—elevated IgG4, other organ involvement (AIP, sialadenitis, retroperitoneal fibrosis), steroid response. Cholangiocarcinoma—dominant stricture, mass, vascular invasion, CA19-9 markedly elevated, no steroid response. Diagnosis: CHOLESTATIC LFTs (↑ALP, GGT, bilirubin). SERUM IgG4 elevated (>135 mg/dL, often >280 mg/dL). IMAGING: MRCP/ERCP—DISTAL COMMON BILE DUCT STRICTURE (60%), hilar/intrahepatic strictures, LONG SEGMENT (>1/3 of bile duct), SMOOTH, SYMMETRIC STENOSIS, PRE-STENOTIC DILATATION. Pancreatic diffuse/focal enlargement (AIP). BILE DUCT BIOPSY/CYTOLOGY: IgG4+ plasma cells >10/HPF, IgG4/IgG ratio >40%. Exclude malignancy (cytology, biopsy). OTHER ORGAN INVOLVEMENT: sialadenitis, retroperitoneal fibrosis, interstitial nephritis. DIAGNOSTIC CRITERIA (HISORt, ICDC). Management: CORTICOSTEROIDS—FIRST-LINE, DRAMATIC RESPONSE. Prednisone 0.6 mg/kg/day x 2-4 weeks, taper over 3-6 months. NORMALIZATION OF LFTs, RESOLUTION OF STRICTURES in 80-90%. RELAPSE common (30-50%) during taper; require maintenance low-dose prednisone, steroid-sparing agents (azathioprine, mycophenolate, rituximab). STEROID-SPARING: azathioprine, mycophenolate, rituximab. STENTING: ERCP with biliary stenting for severe obstructive jaundice (bridge to steroid response). Prognosis: EXCELLENT with steroid therapy. Fibrosis may be irreversible if delayed treatment. Increased risk of malignancy (lymphoma, pancreatic, biliary) but lower than PSC. Zambian context: IgG4-SC is UNRECOGNIZED, misdiagnosed as PSC or cholangiocarcinoma. Think IgG4-SC in OLDER PATIENT with: 1) PAINLESS OBSTRUCTIVE JAUNDICE, 2) DISTAL CBD STRICTURE, 3) PANCREATIC MASS/ENLARGEMENT (AIP), 4) ELEVATED IgG4. Serum IgG4 testing limited. Biopsy (bile duct, pancreas) requires ERCP/EUS expertise. However, a THERAPEUTIC TRIAL OF CORTICOSTEROIDS may be diagnostic and life-saving. Exclude malignancy (cytology, imaging) before steroids. Dramatic response (biochemical, radiographic) confirms diagnosis. Corticosteroids accessible. Azathioprine, mycophenolate accessible. Rituximab unavailable. ERCP/stenting available tertiary centres. High index suspicion.
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Topic 187
Drug-Induced Liver Injury
Drug-induced liver injury (DILI) is an adverse hepatic reaction to medications, herbal products, or dietary supplements, ranging from asymptomatic transaminase elevation to acute liver failure. For Zambian students, DILI is a COMMON and UNDER-RECOGNIZED cause of liver disease, given the high prevalence of anti-tuberculous therapy (ATT), antiretrovirals (ARVs), and traditional herbal medicine use. Pathophysiology: INTRINSIC DILI—dose-dependent, predictable (acetaminophen). IDIOSYNCRATIC DILI—unpredictable, dose-independent, immune-mediated or metabolic. Clinical: HEPATOCELLULAR (predominant ALT elevation, >5x ULN, ALT/ALP ratio >5)—isoniazid, rifampicin, pyrazinamide, nevirapine, efavirenz, fluconazole, statins, NSAIDs, methotrexate, valproate, allopurinol, phenytoin, amoxicillin-clavulanate (mixed). CHOLESTATIC (predominant ALP elevation, ALT/ALP ratio <2)—amoxicillin-clavulanate, chlorpromazine, erythromycin, TMP-SMX, oral contraceptives, anabolic steroids. MIXED (ALT/ALP ratio 2-5). ACUTE LIVER FAILURE (severe hepatocellular injury with coagulopathy, encephalopathy)—acetaminophen (dose-dependent), isoniazid, valproate, phenytoin, halothane, herbal remedies. Diagnosis: HIGH INDEX OF SUSPICION—TEMPORAL ASSOCIATION (drug initiation to onset: days-weeks for most, months for some). EXCLUDE viral hepatitis (A, B, C, E), alcohol, ischemia, autoimmune hepatitis, biliary obstruction. LIVER BIOPSY: not required, but may help exclude other causes, assess severity. CAUSALITY ASSESSMENT: Roussel Uclaf Causality Assessment Method (RUCAM) scale. Management: WITHDRAW OFFENDING AGENT—cornerstone. Most DILI resolves spontaneously with drug cessation. ACETAMINOPHEN OVERDOSE: N-ACETYLCYSTEINE (NAC)—within 8-10h is life-saving; effective up to 24-36h. IDIOSYNCRATIC DILI: no specific antidote. CORTICOSTEROIDS: not routinely indicated; consider for DRESS syndrome, DILI-AIH overlap. ACUTE LIVER FAILURE: NAC (improves transplant-free survival), supportive care, transfer to transplant centre. Prognosis: Most DILI (90%) resolves 2-4 weeks after drug withdrawal. CHOLESTASIS may persist months. Chronic DILI (<5%). Mortality 5-10% (higher with jaundice + hepatocellular injury—Hy's Law). Zambian context: ATT-DILI: isoniazid, rifampicin, pyrazinamide (all potential hepatotoxins). Risk factors: pre-existing liver disease, alcohol, HIV, malnutrition, advanced age. ATT-DILI: Withdraw pyrazinamide (most hepatotoxic), continue isoniazid/rifampicin with close monitoring, reintroduce pyrazinamide after resolution or substitute. ARV-DILI: nevirapine (CD4 >250 women, >400 men, first 12 weeks), efavirenz, protease inhibitors. Nevirapine: substitute with efavirenz. HERBAL REMEDIES: common, underreported. Traditional medicines are a significant cause of DILI in Zambia—ASK every patient. Acetaminophen: widely available; educate on maximum dose (4g/day). NAC available (essential medicine). DILI is a DIAGNOSIS OF EXCLUSION. HIGH INDEX SUSPICION, DETAILED DRUG HISTORY (including OTC, herbs), TIMELY WITHDRAWAL, and MONITORING are life-saving.
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Topic 188Coming soon
Non-Alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, encompassing a spectrum from simple steatosis (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH) with inflammation, hepatocyte injury, and fibrosis, progressing to cirrhosis and hepatocellular carcinoma. For Zambian students, NAFLD is an EMERGING EPIDEMIC in Africa, paralleling the rise in obesity, type 2 diabetes, and metabolic syndrome. It is no longer a 'Western' disease. Pathophysiology: 'MULTIPLE HIT' HYPOTHESIS. HIT 1: INSULIN RESISTANCE → adipose tissue lipolysis, increased free fatty acid flux to liver, hepatic de novo lipogenesis → hepatic steatosis. HIT 2: OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, GUT MICROBIOME, ADIPOKINE/HEPATOKINE DYSREGULATION → hepatocyte injury, inflammation (NASH). HIT 3: activation of hepatic stellate cells → FIBROSIS → CIRRHOSIS. Clinical: ASYMPTOMATIC (90%)—incidental finding of elevated LFTs or hepatic steatosis on imaging. FATIGUE, MALAISE (non-specific). RIGHT UPPER QUADRANT DISCOMFORT (hepatomegaly). SIGNS OF METABOLIC SYNDROME: obesity (visceral adiposity), hypertension, dyslipidaemia (hypertriglyceridaemia, low HDL), prediabetes/type 2 diabetes. CIRRHOSIS: portal hypertension, ascites, variceal haemorrhage, HCC. Diagnosis: HEPATIC STEATOSIS on imaging (ultrasound, CT, MRI-PDFF) OR biopsy. EXCLUSION of significant alcohol consumption (<20 g/day women, <30 g/day men). EXCLUSION of other causes of steatosis/chronic liver disease (viral hepatitis, Wilson's, drugs, hemochromatosis, AIH, PBC/PSC). LIVER BIOPSY: GOLD STANDARD for diagnosis of NASH and staging fibrosis. Indicated if: high risk of NASH/fibrosis (NAFLD fibrosis score, FIB-4, ELF test), competing aetiologies, or clinical trial enrolment. Histology: STEATOSIS (>5% macrovesicular), LOBULAR INFLAMMATION, HEPATOCYTE BALLOONING (NASH), FIBROSIS (perisinusoidal, pericellular 'chicken wire', bridging, cirrhosis). NAFLD ACTIVITY SCORE (NAS), STAGING (Kleiner). NON-INVASIVE MARKERS: FIB-4, NAFLD fibrosis score, APRI, ELF test, transient elastography (FibroScan) with CAP (controlled attenuation parameter). Management: LIFESTYLE MODIFICATION IS CORNERSTONE. WEIGHT LOSS (7-10% of body weight) reduces steatosis, inflammation, and fibrosis. DIET: hypocaloric (500-1000 kcal deficit), Mediterranean diet, reduced carbohydrate/saturated fat, increased fibre. EXERCISE: 150-300 minutes moderate-intensity/week, resistance training. PHARMACOTHERAPY: VITAMIN E (800 IU/day)—improves NASH in non-diabetic, biopsy-proven NASH (no effect on fibrosis). PIOGLITAZONE (30-45 mg/day)—improves NASH, may improve fibrosis in diabetic/pre-diabetic. GLP-1 AGONISTS (liraglutide, semaglutide)—weight loss, improves NASH. OBETICHOLIC ACID, THR-β AGONISTS (resmetirom)—emerging therapies. CIRRHOSIS COMPLICATIONS: screen for varices, HCC surveillance (ultrasound q6 months). LIVER TRANSPLANTATION: for decompensated NASH cirrhosis. Prognosis: NAFL: benign, low risk of cirrhosis (5% over 15y). NASH: progressive fibrosis in 30-40%; cirrhosis in 10-20% over 10-20y; HCC risk (2-4% per year in cirrhosis). Metabolic syndrome, diabetes, ALT elevation, advanced fibrosis predict worse outcomes. Zambian context: NAFLD IS UNDERRECOGNIZED but rapidly increasing. Prevalence of obesity in Zambia: 20-30% urban women. Type 2 diabetes: 5-10%. Think NAFLD in: 1) OVERWEIGHT/OBESE patient with 2) ELEVATED AMINOTRANSFERASES (mild, ALT > AST), 3) HEPATIC STEATOSIS on ultrasound, 4) EXCLUSION of alcohol, viral hepatitis, other causes. Ultrasound is accessible, inexpensive. FIB-4, APRI scores (inexpensive, serum markers) can exclude advanced fibrosis (FIB-4 <1.3, high NPV). Lifestyle modification (diet, exercise) is the ONLY accessible, effective therapy in Zambia. Vitamin E and pioglitazone are available (pioglitazone inexpensive). GLP-1 agonists expensive/unavailable. FibroScan limited (Lusaka). Liver biopsy accessible. HCC surveillance (ultrasound) accessible. PUBLIC HEALTH: prevention of obesity, promotion of physical activity, healthy diet. This is the next wave of chronic liver disease in Zambia. BE PREPARED.
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Coming soon
Topic 189Coming soon
Alcoholic Liver Disease
Alcoholic liver disease (ALD) encompasses a spectrum of liver injury—hepatic steatosis, alcoholic hepatitis, and cirrhosis—caused by chronic excessive alcohol consumption. It remains a leading cause of cirrhosis and liver-related death worldwide and in Zambia. For Zambian students, ALD is HIGHLY PREVALENT and UNDERDIAGNOSED; ABSTINENCE IS LIFE-SAVING. Pathophysiology: ACETALDEHYDE (ethanol metabolite)—direct hepatotoxin, forms protein/DNA adducts, lipid peroxidation, mitochondrial damage, glutathione depletion. CYP2E1 INDUCTION → oxidative stress, reactive oxygen species. GUT-DERIVED ENDOTOXIN → activation of Kupffer cells (TLR4) → TNF-α, IL-1β, IL-6, profibrotic cytokines. Impaired methionine metabolism (↓SAMe). Spectrum: HEPATIC STEATOSIS (90% heavy drinkers)—reversible with abstinence. ALCOHOLIC HEPATITIS (10-35%)—acute-on-chronic inflammatory injury, variable severity, high short-term mortality. CIRRHOSIS (10-20%)—irreversible, micronodular → macronodular, HCC risk (10-15%). Clinical: STEATOSIS: asymptomatic, hepatomegaly. ALCOHOLIC HEPATITIS: JAUNDICE (90%), FEVER (50%), TENDER HEPATOMEGALY, ANOREXIA, MALAISE, WEIGHT LOSS. SEVERE: ascites, encephalopathy, variceal haemorrhage, coagulopathy, acute kidney injury (hepatorenal syndrome), leukocytosis (20-30,000). CIRRHOSIS: signs of portal hypertension, synthetic dysfunction, HCC. Diagnosis: HISTORY OF SIGNIFICANT ALCOHOL CONSUMPTION (≥40-80 g/day, ≥5 years). ELEVATED AST > ALT (2:1), AST <300 IU/L. ELEVATED GGT (sensitive, not specific). MACROCYTOSIS (MCV). ALCOHOLIC HEPATITIS: Maddrey Discriminant Function (DF) = 4.6 x (PT - control) + total bilirubin (mg/dL). DF ≥32 = SEVERE, 30-50% mortality at 28d. MELD score, Glasgow Alcoholic Hepatitis Score (GAHS). LIVER BIOPSY: not always required; shows macrovesicular steatosis, ballooning, Mallory-Denk hyaline, neutrophil infiltration, 'chicken wire' perisinusoidal fibrosis, cirrhosis. EXCLUDE: NAFLD, viral hepatitis, drug-induced, hemochromatosis, Wilson's. Management: ABSTINENCE—CORNERSTONE, ONLY INTERVENTION THAT IMPROVES SURVIVAL. ALCOHOLIC HEPATITIS: SEVERE (DF≥32, GAHS≥9, MELD≥21): CORTICOSTEROIDS (prednisolone 40 mg/day x 28 days, then taper) OR PENTOXIFYLLINE (400 mg TID)—controversial, corticosteroids superior. Lille score (day 7) identifies non-responders (Lille >0.45) → stop steroids. NUTRITIONAL SUPPORT: enteral nutrition (35-40 kcal/kg, 1.2-1.5 g/kg protein) improves survival. AVOID: acetaminophen, NSAIDs, sedatives. CIRRHOSIS COMPLICATIONS: manage ascites (sodium restriction, diuretics, large-volume paracentesis), varices (beta-blockers, band ligation), encephalopathy (lactulose, rifaximin). HCC SURVEILLANCE: ultrasound q6 months. LIVER TRANSPLANTATION: ALCOHOLIC HEPATITIS—selected patients (severe, non-responders, first presentation, favourable psychosocial profile), 6-month abstinence rule (controversial). CIRRHOSIS—6 months abstinence required. Prognosis: STEATOSIS: reversible 2-4 weeks abstinence. ALCOHOLIC HEPATITIS: 30-50% 28d mortality (severe), 50% 1y mortality. CIRRHOSIS: 60-80% 5y survival if abstinent; <50% if continue drinking. Zambian context: ALCOHOL USE DISORDER IS HIGHLY PREVALENT. Alcohol per capita consumption in Zambia is among highest in Africa. ALD is COMMON, STIGMATIZED, UNDERDIAGNOSED, UNDER-TREATED. SCREEN all patients for alcohol use (AUDIT-C, CAGE). Brief intervention, motivational interviewing, referral to alcohol treatment services (where available) are ESSENTIAL. Corticosteroids (prednisolone) accessible, inexpensive. Nutritional support (RUTF, supplementation). Management of cirrhosis complications (diuretics, lactulose, paracentesis) accessible. Variceal band ligation accessible. HCC surveillance accessible. Liver transplant unavailable. Patient, family, community education: ALCOHOL LIVER DISEASE IS PREVENTABLE AND TREATABLE. ABSTINENCE SAVES LIVES. Do not be nihilistic—INTERVENE.